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1

Mitochondrial biogenesis: pharmacological approaches.  

PubMed

Organelle biogenesis is concomitant to organelle inheritance during cell division. It is necessary that organelles double their size and divide to give rise to two identical daughter cells. Mitochondrial biogenesis occurs by growth and division of pre-existing organelles and is temporally coordinated with cell cycle events [1]. However, mitochondrial biogenesis is not only produced in association with cell division. It can be produced in response to an oxidative stimulus, to an increase in the energy requirements of the cells, to exercise training, to electrical stimulation, to hormones, during development, in certain mitochondrial diseases, etc. [2]. Mitochondrial biogenesis is therefore defined as the process via which cells increase their individual mitochondrial mass [3]. Recent discoveries have raised attention to mitochondrial biogenesis as a potential target to treat diseases which up to date do not have an efficient cure. Mitochondria, as the major ROS producer and the major antioxidant producer exert a crucial role within the cell mediating processes such as apoptosis, detoxification, Ca2+ buffering, etc. This pivotal role makes mitochondria a potential target to treat a great variety of diseases. Mitochondrial biogenesis can be pharmacologically manipulated. This issue tries to cover a number of approaches to treat several diseases through triggering mitochondrial biogenesis. It contains recent discoveries in this novel field, focusing on advanced mitochondrial therapies to chronic and degenerative diseases, mitochondrial diseases, lifespan extension, mitohormesis, intracellular signaling, new pharmacological targets and natural therapies. It contributes to the field by covering and gathering the scarcely reported pharmacological approaches in the novel and promising field of mitochondrial biogenesis. There are several diseases that have a mitochondrial origin such as chronic progressive external ophthalmoplegia (CPEO) and the Kearns- Sayre syndrome (KSS), myoclonic epilepsy with ragged-red fibers (MERRF), mitochondrial encephalomyopathy, lactic acidosis and strokelike episodes (MELAS), Leber's hereditary optic neuropathy (LHON), the syndrome of neurogenic muscle weakness, ataxia and retinitis pigmentosa (NARP), and Leigh's syndrome. Likewise, other diseases in which mitochondrial dysfunction plays a very important role include neurodegenerative diseases, diabetes or cancer. Generally, in mitochondrial diseases a mutation in the mitochondrial DNA leads to a loss of functionality of the OXPHOS system and thus to a depletion of ATP and overproduction of ROS, which can, in turn, induce further mtDNA mutations. The work by Yu-Ting Wu, Shi-Bei Wu, and Yau-Huei Wei (Department of Biochemistry and Molecular Biology, National Yang-Ming University, Taiwan) [4] focuses on the aforementioned mitochondrial diseases with special attention to the compensatory mechanisms that prompt mitochondria to produce more energy even under mitochondrial defect-conditions. These compensatory mechanisms include the overexpression of antioxidant enzymes, mitochondrial biogenesis and overexpression of respiratory complex subunits, as well as metabolic shift to glycolysis. The pathways observed to be related to mitochondrial biogenesis as a compensatory adaptation to the energetic deficits in mitochondrial diseases are described (PGC- 1, Sirtuins, AMPK). Several pharmacological strategies to trigger these signaling cascades, according to these authors, are the use of bezafibrate to activate the PPAR-PGC-1? axis, the activation of AMPK by resveratrol and the use of Sirt1 agonists such as quercetin or resveratrol. Other strategies currently used include the addition of antioxidant supplements to the diet (dietary supplementation with antioxidants) such as L-carnitine, coenzyme Q10,MitoQ10 and other mitochondria-targeted antioxidants,N-acetylcysteine (NAC), vitamin C, vitamin E vitamin K1, vitamin B, sodium pyruvate or -lipoic acid. As aforementioned, other diseases do not have exclusively a mitochondrial origin but they might have an importan

Valero, Teresa

2014-01-01

2

MITOCHONDRIAL BIOGENESIS AND HEALTHY AGING  

PubMed Central

Aging is associated with an overall loss of function at the level of the whole organism that has origins in cellular deterioration. Most cellular components, including mitochondria, require continuous recycling and regeneration throughout the lifespan. Mitochondria are particularly susceptive to damage over time as they are the major bioenergetic machinery and source of oxidative stress in cells. Effective control of mitochondrial biogenesis and turnover, therefore, becomes critical for the maintenance of energy production, the prevention of endogenous oxidative stress and the promotion of healthy aging. Multiple endogenous and exogenous factors regulate mitochondrial biogenesis through the peroxisome proliferator-activated receptor gamma coactivator-1? (PGC-1?). Activators of PGC-1? include nitric oxide, CREB and AMPK. Calorie restriction (CR) and resveratrol, a proposed CR mimetic, also increase mitochondrial biogenesis through activation of PGC-1?. Moderate exercise also mimics CR by inducing mitochondrial biogenesis. Negative regulators of PGC-1? such as RIP140 and 160MBP suppress mitochondrial biogenesis. Another mechanism involved in mitochondrial maintenance is mitochondrial fission/fusion and this process also involves an increasing number of regulatory proteins. Dysfunction of either biogenesis or fission/fusion of mitochondria is associated with diseases of the neuromuscular system and aging, and a greater understanding of the regulation of these processes should help us to ultimately control the aging process. PMID:18662766

López-Lluch, Guillermo; Irusta, Pablo M.; Navas, Placido; de Cabo, Rafael

2008-01-01

3

Redox Regulation of Mitochondrial Biogenesis  

PubMed Central

Background The cell renews, adapts, or expands its mitochondrial population during episodes of cell damage or periods of intensified energy demand by the induction of mitochondrial biogenesis. This bi-genomic program is modulated by redox-sensitive signals that respond to physiological nitric oxide (NO), carbon monoxide (CO), and mitochondrial reactive oxygen species (ROS) production. Scope of Review This review summarizes our current ideas about the pathways involved in the activation of mitochondrial biogenesis by the physiological gases leading to changes in the redox milieu of the cell with an emphasis on the responses to oxidative stress and inflammation. Major Conclusions The cell’s energy supply is protected from conditions that damage mitochondria by an inducible transcriptional program of mitochondrial biogenesis that operates in large part through redox signals involving the nitric oxide synthase and the heme oxygenase-1/CO systems. These redox events stimulate the coordinated activities of several multifunctional transcription factors and co-activators also involved in the elimination of defective mitochondria and the expression of counter-inflammatory and anti-oxidant genes, such as IL10 and Sod2, as part of a unified damage-control network. General Significance The redox-regulated mechanisms of mitochondrial biogenesis schematically outlined in the graphical abstract link mitochondrial quality control to an enhanced capacity to support the cell’s metabolic needs while improving its resistance to metabolic failure and avoidance of cell death during periods of oxidative stress. PMID:23000245

Piantadosi, Claude A.; Suliman, Hagir B.

2013-01-01

4

Unique aspects of mitochondrial biogenesis in trypanosomatids  

Microsoft Academic Search

Mitochondrial biogenesis consists of the sum of all processes required for the formation of the mitochondrial membranes as well as the soluble compartments they contain. Furthermore, it includes the replication of the mitochondrial genome and correct segregation of the organelles during cell division. Mitochondrial proteins come from two sources, a limited but essential set of inner membrane proteins is encoded

André Schneider

2001-01-01

5

Mitochondrial biogenesis in plants during seed germination.  

PubMed

Mitochondria occupy a central role in the eukaryotic cell. In addition to being major sources of cellular energy, mitochondria are also involved in a diverse range of functions including signalling, the synthesis of many essential organic compounds and a role in programmed cell death. The active proliferation and differentiation of mitochondria is termed mitochondrial biogenesis and necessitates the coordinated communication of mitochondrial status within an integrated cellular network. Two models of mitochondrial biogenesis have been defined previously, the growth and division model and the maturation model. The former describes the growth and division of pre-existing mature organelles through a form of binary fission, while the latter describes the propagation of mitochondria from structurally and biochemically simple promitochondrial structures that upon appropriate stimuli, mature into fully functional mitochondria. In the last decade, a number of studies have utilised seed germination in plants as a platform for the examination of the processes occurring during mitochondrial biogenesis. These studies have revealed many new aspects of the tightly regulated procession of events that define mitochondrial biogenesis during this period of rapid development. A model for mitochondrial biogenesis that supports the maturation of mitochondria from promitochondrial structures has emerged, where mitochondrial signalling plays a crucial role in the early steps of seed germination. PMID:24727594

Law, Simon R; Narsai, Reena; Whelan, James

2014-11-01

6

Interactions between bioenergetics and mitochondrial biogenesis  

Microsoft Academic Search

We studied the interaction between energy metabolism and mitochondrial biogenesis during myogenesis in C2C12 myoblasts. Metabolic rate was nearly constant throughout differentiation, although there was a shift in the relative importance of glycolytic and oxidative metabolism, accompanied by increases in pyruvate dehydrogenase activation state and total activity. These changes in mitochondrial bioenergetic parameters observed during differentiation occurred in the absence

Scot C. Leary; Brendan J. Battersby; Richard G. Hansford; Christopher D. Moyes

1998-01-01

7

Mitochondrial nutrients stimulate performance and mitochondrial biogenesis in exhaustively exercised rats.  

PubMed

The aim of this study was to investigate the effects of a combination of nutrients on physical performance, oxidative stress and mitochondrial biogenesis in rats subjected to exhaustive exercise. Rats were divided into sedentary control (SC), exhaustive exercise (EC) and exhaustive exercise with nutrient supplementation (EN). The nutrients include (mg/kg/day): R-?-lipoic acid 50, acetyl-L-carnitine 100, biotin 0.1, nicotinamide 15, riboflavin 6, pyridoxine 6, creatine 50, CoQ10 5, resveratrol 5 and taurine 100. Examination of running distances over the 4-week period revealed that EN rats ran significantly longer throughout the entire duration of the exhaustive exercise period compared with the EC rats. Nutrient supplementation significantly inhibited the increase in activities of alanine transaminase, lactate dehydrogenase and creatine kinase, reversed increases in malondialdehyde, inhibited decreases in glutathione S-transferase and total antioxidant capacity in plasma, and suppressed the elevation of reactive oxygen species and apoptosis in splenic lymphocytes. Nutrient supplementation increased the protein expression of mitochondrial complexes I, II and III, mtDNA number and transcription factors involved in mitochondrial biogenesis and fusion in skeletal muscle. These findings suggest that mitochondrial nutrient supplementation can reduce exhaustive exercise-induced oxidative damage and mitochondrial dysfunction, thus leading to enhancement of physical performance and of fatigue recovery. PMID:21507065

Sun, M; Qian, F; Shen, W; Tian, C; Hao, J; Sun, L; Liu, J

2012-12-01

8

Mitochondrial biogenesis defects and neuromuscular disorders  

Microsoft Academic Search

A variety of mitochondrial DNA (mtDNA) defects, ranging from point mutations and large-scale deletions to severe reduction in the overall quantity of mtDNA (mtDNA depletion), may be associated with neuromuscular disorders. The nuclear genome, which encodes most of the proteins involved in mitochondrial biogenesis (regulation of maintenance, replication, and transcription of mtDNA), appears to be implicated in many of the

Jose Marin-Garcia; Michael J Goldenthal

2000-01-01

9

Mitochondrial dynamic remodeling in strenuous exercise-induced muscle and mitochondrial dysfunction: regulatory effects of hydroxytyrosol.  

PubMed

Physical exercise is considered to exert a positive effect on health, whereas strenuous or excessive exercise (Exe) causes fatigue and damage to muscle and immune functions. The underlying molecular mechanisms are still unclear. We designed a protocol to mimic Exe and explore the ensuing cellular damage and involvement of mitochondrial dynamics. We found that Exe was prone to decrease endurance capacity and induce damage to renal function and the immune system. Muscle atrophy markers atrogin-1 and MuRF1 mRNA were increased by Exe, accompanied by increased autophagy and mitochondrial fission in skeletal muscle. Exe caused a decrease in PGC-1? and complex I expression; it also activated JNK and Erk1/2 pathways and consequently induced p53, p21, and MnSOD expression in skeletal muscle. The involvement of oxidant-induced autophagy and mitochondrial dysfunction was confirmed in C2C12 myoblasts. Hydroxytyrosol (HT), a natural olive polyphenol, efficiently enhanced endurance capacity and prevented Exe-induced renal and immune system damage. Also, HT treatment inhibited both the Exe-induced increase in autophagy and mitochondrial fission and the decrease in PGC-1? expression. In addition, HT enhanced mitochondrial fusion and mitochondrial complex I and II activities in muscle of Exe rats. These results demonstrate that Exe-induced fatigue and damage to muscle and immune functions may be mediated via the regulation of mitochondrial dynamic remodeling, including the downregulation of mitochondrial biogenesis and upregulation of autophagy. HT supplementation may regulate mitochondrial dynamic remodeling and enhance antioxidant defenses and thus improve exercise capacity under Exe conditions. PMID:21421045

Feng, Zhihui; Bai, Liyuan; Yan, Jiong; Li, Yuan; Shen, Weili; Wang, Ying; Wertz, Karin; Weber, Peter; Zhang, Yong; Chen, Yan; Liu, Jiankang

2011-05-15

10

Mitochondrial Biogenesis during Germination in Maize Embryos  

Microsoft Academic Search

Mitochondrial biogenesis and metabolism were investigated during maize (Zea mays) seed germination. Mitochondria from dry and imbibed seed exhibited NADH-dependent O2 uptake that was completely inhibited by KCN and antimycin A. Mitochondria in the dry seed had a lower rate of succinate-dependent O2 uptake relative to that measured in imbibed and germinated seed. The activities of the tricarboxylic acid (TCA)

David C. Logan; A. Harvey Millar; Lee J. Sweetlove; Steven A. Hill; Christopher J. Leaver

2001-01-01

11

Mitochondrial Biogenesis in Mammals: The Role of Endogenous Nitric Oxide  

Microsoft Academic Search

Nitric oxide was found to trigger mitochondrial biogenesis in cells as diverse as brown adipocytes and 3T3-L1, U937, and HeLa cells. This effect of nitric oxide was dependent on guanosine 3',5'-monophosphate (cGMP) and was mediated by the induction of peroxisome proliferator-activated receptor gamma coactivator 1alpha, a master regulator of mitochondrial biogenesis. Moreover, the mitochondrial biogenesis induced by exposure to cold

Enzo Nisoli; Emilio Clementi; Clara Paolucci; Valeria Cozzi; Cristina Tonello; Clara Sciorati; Renata Bracale; Alessandra Valerio; Maura Francolini; Salvador Moncada; Michele O. Carruba

2003-01-01

12

Spatio-Temporal Dynamics of Yeast Mitochondrial Biogenesis: Transcriptional and Post-Transcriptional  

E-print Network

Spatio-Temporal Dynamics of Yeast Mitochondrial Biogenesis: Transcriptional and Post that unknown genes from this module code for important elements of mitochondrial biogenesis is supported-transcriptional processes in mitochondrial biogenesis, highlighting close connections between nuclear transcription

Boyer, Edmond

13

Reperfusion Promotes Mitochondrial Biogenesis following Focal Cerebral Ischemia in Rats  

PubMed Central

Background and Purpose Reperfusion after transient cerebral ischemia causes severe damage to mitochondria; however, little is known regarding the continuous change in mitochondrial biogenesis during reperfusion. Mitochondrial biogenesis causes an increase in the individual mitochondrial mass of neurons and maintains their aerobic set-point in the face of declining function. The aim of this study was to examine mitochondrial biogenesis in the cortex during reperfusion following focal cerebral ischemia. Methods Male Wistar rats were subjected to transient focal cerebral ischemia. The relative amount of cortical mitochondrial DNA was analyzed using quantitative real-time PCR at 0 h, 24 h, 72 h, and 7 d after reperfusion. Three critical transcriptional regulators of mitochondrial biogenesis were measured by semi-quantitative reverse-transcription PCR. The protein expression of cytochrome C oxidase subunits I and IV was detected by Western blotting. Results Evidence of increased mitochondrial biogenesis was observed after reperfusion. The cortical mitochondrial DNA content increased after 24 h, peaked after 72 h, and maintained a high level for 7 d. The cortical expression of three critical genes for the transcriptional regulation of mitochondrial biogenesis, namely, peroxisome proliferator-activated receptor coactivator-1?, nuclear respiratory factor-1, and mitochondrial transcription factor A, also increased at 24 h and 72 h. The expression of peroxisome proliferator-activated receptor coactivator-1? returned to the baseline level at 7 d, but two other factors maintained higher levels compared with the controls. Moreover, the expression of cytochrome C oxidase subunits I and IV was increased in the cortex. Conclusions These results indicate that reperfusion increased mitochondrial biogenesis following focal cerebral ischemia, and this tendency was exacerbated as the reperfusion time was extended. Reperfusion-induced mitochondrial biogenesis was mediated through up-regulation of critical transcriptional regulators of mitochondrial biogenesis. PMID:24667167

Xie, Yuying; Li, Jun; Fan, Guibo; Qi, Sihua; Li, Bing

2014-01-01

14

Coordination of Nuclear and Mitochondrial Genome Expression during Mitochondrial Biogenesis in Arabidopsis  

Microsoft Academic Search

Mitochondrial biogenesis and function require the regulated and coordinated expression of nuclear and mitochondrial genomes throughout plant development and in response to cellular and environmental signals. To investigate the levels at which the expression of nuclear and mitochondrially encoded proteins is coordinated, we established an Arabidopsis thaliana cell culture system to modulate mitochondrial biogenesis in response to sugar starvation and

Philippe Giege; Lee J. Sweetlove; Valerie Cognat; Christopher J. Leaverb

2005-01-01

15

Mitochondrial biogenesis: which part of ``NO'' do we understand?  

E-print Network

Mitochondrial biogenesis: which part of ``NO'' do we understand? Scot C. Leary and Eric. A), a master regulator of mitochondrial content. These results raise intriguing possibilities for a role of NO in modulating mitochondrial content in response to physiological stimuli such as exercise or cold exposure

Leary, Scot

16

Nuclear activators and coactivators in mammalian mitochondrial biogenesis  

Microsoft Academic Search

The biogenesis of mitochondria requires the expression of a large number of genes, most of which reside in the nuclear genome. The protein-coding capacity of mtDNA is limited to 13 respiratory subunits necessitating that nuclear regulatory factors play an important role in governing nucleo-mitochondrial interactions. Two classes of nuclear transcriptional regulators implicated in mitochondrial biogenesis have emerged in recent years.

Richard C Scarpulla

2002-01-01

17

Successive bouts of cycling stimulates genes associated with mitochondrial biogenesis  

Microsoft Academic Search

Exercise increases mRNA for genes involved in mitochondrial biogenesis and oxidative enzyme capacity. However, little is known\\u000a about how these genes respond to consecutive bouts of prolonged exercise. We examined the effects of 3 h of intensive cycling\\u000a performed on three consecutive days on the mRNA associated with mitochondrial biogenesis in trained human subjects. Forty\\u000a trained cyclists were tested for VO2max

Charles L. Dumke; J. Mark Davis; E. Angela Murphy; David C. Nieman; Martin D. Carmichael; John C. Quindry; N. Travis Triplett; Alan C. Utter; Sarah J. Gross Gowin; Dru A. Henson; Steven R. McAnulty; Lisa S. McAnulty

2009-01-01

18

Mitochondrial biogenesis by NO yields functionally active mitochondria in mammals  

Microsoft Academic Search

We recently found that long-term exposure to nitric oxide (NO) triggers mitochondrial biogenesis in mammalian cells and tissues by activation of guanylate cyclase and generation of cGMP. Here, we report that the NO\\/cGMP-dependent mitochondrial biogenesis is associated with enhanced coupled respiration and content of ATP in U937, L6, and PC12 cells. The observed increase in ATP content depended entirely on

Enzo Nisoli; Sestina Falcone; Cristina Tonello; Valeria Cozzi; Letizia Palomba; Mara Fiorani; Addolorata Pisconti; Silvia Brunelli; Annalisa Cardile; Maura Francolini; Orazio Cantoni; Michele O. Carruba; Salvador Moncada; Emilio Clementi

2004-01-01

19

Hyperglycemia decreases mitochondrial function: The regulatory role of mitochondrial biogenesis  

SciTech Connect

Increased generation of reactive oxygen species (ROS) is implicated in 'glucose toxicity' in diabetes. However, little is known about the action of glucose on the expression of transcription factors in hepatocytes, especially those involved in mitochondrial DNA (mtDNA) replication and transcription. Since mitochondrial functional capacity is dynamically regulated, we hypothesized that stressful conditions of hyperglycemia induce adaptations in the transcriptional control of cellular energy metabolism, including inhibition of mitochondrial biogenesis and oxidative metabolism. Cell viability, mitochondrial respiration, ROS generation and oxidized proteins were determined in HepG2 cells cultured in the presence of either 5.5 mM (control) or 30 mM glucose (high glucose) for 48 h, 96 h and 7 days. Additionally, mtDNA abundance, plasminogen activator inhibitor-1 (PAI-1), mitochondrial transcription factor A (TFAM) and nuclear respiratory factor-1 (NRF-1) transcripts were evaluated by real time PCR. High glucose induced a progressive increase in ROS generation and accumulation of oxidized proteins, with no changes in cell viability. Increased expression of PAI-1 was observed as early as 96 h of exposure to high glucose. After 7 days in hyperglycemia, HepG2 cells exhibited inhibited uncoupled respiration and decreased MitoTracker Red fluorescence associated with a 25% decrease in mtDNA and 16% decrease in TFAM transcripts. These results indicate that glucose may regulate mtDNA copy number by modulating the transcriptional activity of TFAM in response to hyperglycemia-induced ROS production. The decrease of mtDNA content and inhibition of mitochondrial function may be pathogenic hallmarks in the altered metabolic status associated with diabetes.

Palmeira, Carlos M. [Center for Neurosciences and Cell Biology of Coimbra, Department of Zoology, University of Coimbra, 3004-517 Coimbra (Portugal)], E-mail: palmeira@ci.uc.pt; Rolo, Anabela P. [Center for Neurosciences and Cell Biology of Coimbra, Department of Zoology, University of Coimbra, 3004-517 Coimbra (Portugal); Berthiaume, Jessica; Bjork, James A.; Wallace, Kendall B. [Department of Biochemistry and Molecular Biology, University of Minnesota School of Medicine, Duluth, MN (United States)

2007-12-01

20

Glucocorticoid Hormone Stimulates Mitochondrial Biogenesis Specifically in Skeletal Muscle  

Microsoft Academic Search

High levels of circulating glucocorticoid hormone may be im- portant mediators for elevating resting metabolic rate upon severe injury or stress. We therefore investigated the effect of dexamethasone on mitochondrial biogenesis in rats (6 mg\\/kg daily) as well as in cells in culture (1 M) over a period of 3 d. A marked stimulation of mitochondrial DNA transcription and increased

KATHARINA WEBER; PATRICK BRUCK; ZSUZSANNA MIKES; JAN-HEINER KUPPER; MARTIN KLINGENSPOR; RUDOLF J. WIESNER

2002-01-01

21

Molecular Genetics of Mitochondrial Biogenesis in Maize.  

Technology Transfer Automated Retrieval System (TEKTRAN)

The mitochondrial genome encodes proteins essential for mitochondrial respiration and ATP synthesis. Nuclear gene products, however, are required for the expression of mitochondrial genes and the elaboration of functional mitochondrial protein complexes. We are exploiting a unique collection of maiz...

22

The role of protein degradation in mitochondrial function and biogenesis  

Microsoft Academic Search

It has been known for a long time that mitochondria contain their own protein-degradation systems. Only recently, however,\\u000a have genes for mitochondrial proteases been identified and the powerful techniques of molecular biology been applied to gain\\u000a insight into the role of protein degradation in mitochondrial biogenesis. It is now clear that the mitochondrial proteases\\u000a that are involved in the initial

M. Rep; L. A. Grivell

1996-01-01

23

After the banquet: mitochondrial biogenesis, mitophagy, and cell survival.  

PubMed

Mitochondria are highly dynamic organelles of crucial importance to the proper functioning of neuronal, cardiac and other cell types dependent upon aerobic efficiency. Mitochondrial dysfunction has been implicated in numerous human conditions, to include cancer, metabolic diseases, neurodegeneration, diabetes, and aging. In recent years, mitochondrial turnover by macroautophagy (mitophagy) has captured the limelight, due in part to discoveries that genes linked to Parkinson disease regulate this quality control process. A rapidly growing literature is clarifying effector mechanisms that underlie the process of mitophagy; however, factors that regulate positive or negative cellular outcomes have been less studied. Here, we review the literature on two major pathways that together may determine cellular adaptation vs. cell death in response to mitochondrial dysfunction. Mitochondrial biogenesis and mitophagy represent two opposing, but coordinated processes that determine mitochondrial content, structure, and function. Recent data indicate that the capacity to undergo mitochondrial biogenesis, which is dysregulated in disease states, may play a key role in determining cell survival following mitophagy-inducing injuries. The current literature on major pathways that regulate mitophagy and mitochondrial biogenesis is summarized, and mechanisms by which the interplay of these two processes may determine cell fate are discussed. We conclude that in primary neurons and other mitochondrially dependent cells, disruptions in any phase of the mitochondrial recycling process can contribute to cellular dysfunction and disease. Given the emerging importance of crosstalk among regulators of mitochondrial function, autophagy, and biogenesis, signaling pathways that coordinate these processes may contribute to therapeutic strategies that target or regulate mitochondrial turnover and regeneration. PMID:23787782

Zhu, Jianhui; Wang, Kent Z Q; Chu, Charleen T

2013-11-01

24

Ssq1, a Mitochondrial Hsp70 Involved in Iron-Sulfur (Fe/S) Center Biogenesis  

E-print Network

Ssq1, a Mitochondrial Hsp70 Involved in Iron-Sulfur (Fe/S) Center Biogenesis SIMILARITIES function together to assist in the biogenesis of iron- sulfur (Fe/S) centers in the mitochondrial matrix iron level (4­8). Mitochondrial pro- teins functioning in biogenesis of Fe/S centers are related

Craig, Elizabeth A

25

Echinochrome a increases mitochondrial mass and function by modulating mitochondrial biogenesis regulatory genes.  

PubMed

Echinochrome A (Ech A) is a natural pigment from sea urchins that has been reported to have antioxidant properties and a cardio protective effect against ischemia reperfusion injury. In this study, we ascertained whether Ech A enhances the mitochondrial biogenesis and oxidative phosphorylation in rat cardio myoblast H9c2 cells. To study the effects of Ech A on mitochondrial biogenesis, we measured mitochondrial mass, level of oxidative phosphorylation, and mitochondrial biogenesis regulatory gene expression. Ech A treatment did not induce cytotoxicity. However, Ech A treatment enhanced oxygen consumption rate and mitochondrial ATP level. Likewise, Ech A treatment increased mitochondrial contents in H9c2 cells. Furthermore, Ech A treatment up-regulated biogenesis of regulatory transcription genes, including proliferator-activated receptor gamma co-activator (PGC)-1?, estrogen-related receptor (ERR)-?, peroxisome proliferator-activator receptor (PPAR)-?, and nuclear respiratory factor (NRF)-1 and such mitochondrial transcription regulatory genes as mitochondrial transcriptional factor A (TFAM), mitochondrial transcription factor B2 (TFB2M), mitochondrial DNA direct polymerase (POLMRT), single strand binding protein (SSBP) and Tu translation elongation factor (TUFM). In conclusion, these data suggest that Ech A is a potentiated marine drug which enhances mitochondrial biogenesis. PMID:25196935

Jeong, Seung Hun; Kim, Hyoung Kyu; Song, In-Sung; Noh, Su Jin; Marquez, Jubert; Ko, Kyung Soo; Rhee, Byoung Doo; Kim, Nari; Mishchenko, Natalia P; Fedoreyev, Sergey A; Stonik, Valentin A; Han, Jin

2014-08-01

26

Echinochrome A Increases Mitochondrial Mass and Function by Modulating Mitochondrial Biogenesis Regulatory Genes  

PubMed Central

Echinochrome A (Ech A) is a natural pigment from sea urchins that has been reported to have antioxidant properties and a cardio protective effect against ischemia reperfusion injury. In this study, we ascertained whether Ech A enhances the mitochondrial biogenesis and oxidative phosphorylation in rat cardio myoblast H9c2 cells. To study the effects of Ech A on mitochondrial biogenesis, we measured mitochondrial mass, level of oxidative phosphorylation, and mitochondrial biogenesis regulatory gene expression. Ech A treatment did not induce cytotoxicity. However, Ech A treatment enhanced oxygen consumption rate and mitochondrial ATP level. Likewise, Ech A treatment increased mitochondrial contents in H9c2 cells. Furthermore, Ech A treatment up-regulated biogenesis of regulatory transcription genes, including proliferator-activated receptor gamma co-activator (PGC)-1?, estrogen-related receptor (ERR)-?, peroxisome proliferator-activator receptor (PPAR)-?, and nuclear respiratory factor (NRF)-1 and such mitochondrial transcription regulatory genes as mitochondrial transcriptional factor A (TFAM), mitochondrial transcription factor B2 (TFB2M), mitochondrial DNA direct polymerase (POLMRT), single strand binding protein (SSBP) and Tu translation elongation factor (TUFM). In conclusion, these data suggest that Ech A is a potentiated marine drug which enhances mitochondrial biogenesis. PMID:25196935

Jeong, Seung Hun; Kim, Hyoung Kyu; Song, In-Sung; Noh, Su Jin; Marquez, Jubert; Ko, Kyung Soo; Rhee, Byoung Doo; Kim, Nari; Mishchenko, Natalia P.; Fedoreyev, Sergey A.; Stonik, Valentin A.; Han, Jin

2014-01-01

27

Exercise-induced heart mitochondrial cholesterol depletion influences the inhibition of mitochondrial swelling.  

PubMed

The significance of the reduction of the cholesterol pool in heart mitochondria after exercise is still unknown. Recently, published data have suggested that cholesterol may influence the components of mitochondrial contact site and affect mitochondrial swelling. Therefore, the aim of this study was to determine whether the decreased cholesterol content in heart mitochondria caused by prolonged swimming may provoke changes in their bioenergetics and result in an increased resistance to calcium chloride-induced mitochondrial swelling. Male Wistar rats were divided into a sedentary control group and an exercise group. The rats exercised for 3 h, burdened with an additional 3% of their body weight. Their hearts were removed immediately after completing the exercise. The left ventricle was divided and used for experiments. Mitochondrial cholesterol content, membrane fluidity and mitochondrial bioenergetics were measured in the control and exercised rat heart mitochondria. To assess whether mitochondrial modifications are linked to disruption of lipid microdomains, methyl-?-cyclodextrin, a well-known lipid microdomain-disrupting agent and cholesterol chelator, was applied to the mitochondria of the control group. Cholesterol depletion, increased membrane fluidity and increased resistance to calcium chloride-induced swelling were observed in postexercise heart crude mitochondrial fraction. Similar results were achieved in control mitochondria treated with 2% methyl-?-cyclodextrin. All of the mitochondrial bioenergetics parameters were similar between the groups. Therefore, the disruption of raft-like microdomains appears to be an adaptive change in the rat heart following exercise. PMID:23733522

Ziolkowski, Wieslaw; Vadhana M S, Dhivya; Kaczor, Jan Jacek; Olek, Robert Antoni; Flis, Damian Jozef; Halon, Malgorzata; Wozniak, Michal; Fedeli, Donatella; Carloni, Manuel; Antosiewicz, Jedrzej; Gabbianelli, Rosita

2013-10-01

28

Lipopolysaccharide induces oxidative cardiac mitochondrial damage and biogenesis  

Microsoft Academic Search

Abstract Objective: The responses to bacterial lipopolysaccharide (LPS) damage,mitochondria by generating oxidative stress within the organelles. We postulated that LPS damages heart mitochondrial DNA and protein by oxidation, and that this is recovered by oxidative mechanisms of mitochondrial biogenesis. Methods and results: Systemic crude E. coli LPS administration decreased mtDNA copy number,and mtDNA gene transcription in rat heart caused by

Hagir B. Suliman; Karen E. Welty-Wolf; Martha Sue Carraway; Lynn Tatro; Claude A. Piantadosi

29

Mitochondrial Dysregulation in the Pathogenesis of Diabetes: Potential for Mitochondrial Biogenesis-Mediated Interventions  

PubMed Central

Muscle mitochondrial metabolism is a tightly controlled process that involves the coordination of signaling pathways and factors from both the nuclear and mitochondrial genomes. Perhaps the most important pathway regulating metabolism in muscle is mitochondrial biogenesis. In response to physiological stimuli such as exercise, retrograde signaling pathways are activated that allow crosstalk between the nucleus and mitochondria, upregulating hundreds of genes and leading to higher mitochondrial content and increased oxidation of substrates. With type 2 diabetes, these processes can become dysregulated and the ability of the cell to respond to nutrient and energy fluctuations is diminished. This, coupled with reduced mitochondrial content and altered mitochondrial morphology, has been directly linked to the pathogenesis of this disease. In this paper, we will discuss our current understanding of mitochondrial dysregulation in skeletal muscle as it relates to type 2 diabetes, placing particular emphasis on the pathways of mitochondrial biogenesis and mitochondrial dynamics, and the therapeutic value of exercise and other interventions. PMID:22203837

Joseph, Anna-Maria; Joanisse, Denis R.; Baillot, Richard G.; Hood, David A.

2012-01-01

30

Selenite stimulates mitochondrial biogenesis signaling and enhances mitochondrial functional performance in murine hippocampal neuronal cells.  

PubMed

Supplementation of selenium has been shown to protect cells against free radical mediated cell damage. The objectives of this study are to examine whether supplementation of selenium stimulates mitochondrial biogenesis signaling pathways and whether selenium enhances mitochondrial functional performance. Murine hippocampal neuronal HT22 cells were treated with sodium selenite for 24 hours. Mitochondrial biogenesis markers, mitochondrial respiratory rate and activities of mitochondrial electron transport chain complexes were measured and compared to non-treated cells. The results revealed that treatment of selenium to the HT22 cells elevated the levels of nuclear mitochondrial biogenesis regulators PGC-1? and NRF1, as well as mitochondrial proteins cytochrome c and cytochrome c oxidase IV (COX IV). These effects are associated with phosphorylation of Akt and cAMP response element-binding (CREB). Supplementation of selenium significantly increased mitochondrial respiration and improved the activities of mitochondrial respiratory complexes. We conclude that selenium activates mitochondrial biogenesis signaling pathway and improves mitochondrial function. These effects may be associated with modulation of AKT-CREB pathway. PMID:23110128

Mendelev, Natalia; Mehta, Suresh L; Idris, Haza; Kumari, Santosh; Li, P Andy

2012-01-01

31

Selenite Stimulates Mitochondrial Biogenesis Signaling and Enhances Mitochondrial Functional Performance in Murine Hippocampal Neuronal Cells  

PubMed Central

Supplementation of selenium has been shown to protect cells against free radical mediated cell damage. The objectives of this study are to examine whether supplementation of selenium stimulates mitochondrial biogenesis signaling pathways and whether selenium enhances mitochondrial functional performance. Murine hippocampal neuronal HT22 cells were treated with sodium selenite for 24 hours. Mitochondrial biogenesis markers, mitochondrial respiratory rate and activities of mitochondrial electron transport chain complexes were measured and compared to non-treated cells. The results revealed that treatment of selenium to the HT22 cells elevated the levels of nuclear mitochondrial biogenesis regulators PGC-1? and NRF1, as well as mitochondrial proteins cytochrome c and cytochrome c oxidase IV (COX IV). These effects are associated with phosphorylation of Akt and cAMP response element-binding (CREB). Supplementation of selenium significantly increased mitochondrial respiration and improved the activities of mitochondrial respiratory complexes. We conclude that selenium activates mitochondrial biogenesis signaling pathway and improves mitochondrial function. These effects may be associated with modulation of AKT-CREB pathway. PMID:23110128

Idris, Haza; Kumari, Santosh; Li, P. Andy

2012-01-01

32

Folding and Biogenesis of Mitochondrial Small Tim Proteins  

PubMed Central

Correct and timely folding is critical to the function of all proteins. The importance of this is illustrated in the biogenesis of the mitochondrial intermembrane space (IMS) “small Tim” proteins. Biogenesis of the small Tim proteins is regulated by dedicated systems or pathways, beginning with synthesis in the cytosol and ending with assembly of individually folded proteins into functional complexes in the mitochondrial IMS. The process is mostly centered on regulating the redox states of the conserved cysteine residues: oxidative folding is crucial for protein function in the IMS, but oxidized (disulfide bonded) proteins cannot be imported into mitochondria. How the redox-sensitive small Tim precursor proteins are maintained in a reduced, import-competent form in the cytosol is not well understood. Recent studies suggest that zinc and the cytosolic thioredoxin system play a role in the biogenesis of these proteins. In the IMS, the mitochondrial import and assembly (MIA) pathway catalyzes both import into the IMS and oxidative folding of the small Tim proteins. Finally, assembly of the small Tim complexes is a multistep process driven by electrostatic and hydrophobic interactions; however, the chaperone function of the complex might require destabilization of these interactions to accommodate the substrate. Here, we review how folding of the small Tim proteins is regulated during their biogenesis, from maintenance of the unfolded precursors in the cytosol, to their import, oxidative folding, complex assembly and function in the IMS. PMID:23945562

Ceh-Pavia, Efrain; Spiller, Michael P.; Lu, Hui

2013-01-01

33

Mitochondrial biogenesis and mitochondrial DNA maintenance of mammalian cells under oxidative stress  

Microsoft Academic Search

Mitochondrial biogenesis and mitochondrial DNA (mtDNA) maintenance depend on coordinated expression of genes in the nucleus and mitochondria. A variety of intracellular and extracellular signals transmitted by hormones and second messengers have to be integrated to provide mammalian cells with a suitable abundance of mitochondria and mtDNA to meet their energy demand. It has been proposed that reactive oxygen species

Hsin-Chen Lee; Yau-Huei Wei

2005-01-01

34

Upregulation of human selenoprotein H in murine hippocampal neuronal cells promotes mitochondrial biogenesis and functional performance.  

PubMed

Overexpression of selenoprotein H (SelH) gene provides neuroprotection in neurons against UVB-induced cell death by blocking the mitochondrial-initiated apoptotic cell death pathway. This study examined the effects of SelH on mitochondrial biogenesis and mitochondrial function. The results demonstrated that overexpression of SelH gene in neuronal HT22 cells significantly increased the levels of mitochondrial biogenesis regulators, nuclear respiratory factor-1 (NRF-1), peroxisome proliferator-activated receptor-? coactivator-1 alpha (PGC-1?) and mitochondrial transcription factor A (Tfam). Mitochondrial cytochrome c content was elevated, mass was increased and respiration was enhanced. SelH transfection ameliorated ultra violet B (UVB)-induced suppression of mitochondrial biogenesis markers and depolarization of mitochondrial membrane potential. Overexpression of SelH promotes mitochondrial biogenesis and improves mitochondrial functional performance. PMID:20656065

Mendelev, Natalia; Mehta, Suresh L; Witherspoon, Sam; He, Qingping; Sexton, Jonathan Z; Li, P Andy

2011-01-01

35

Mitochondrial biogenesis as a cellular signaling framework  

Microsoft Academic Search

The identification, more than 50 years ago, of mitochondria as the site of oxidative energy metabolism has prompted studies that have unraveled the complexity of the numerous biosynthetic and degradative reactions, fundamental to cell function, carried out by these organelles. These activities depend on a distinctive mitochondrial structure, with different enzymes and reactions localized in discrete membranes and aqueous compartments.

Enzo Nisoli; Emilio Clementi; Salvador Moncada; Michele O. Carruba

2004-01-01

36

Staphylococcus aureus Sepsis Induces Early Renal Mitochondrial DNA Repair and Mitochondrial Biogenesis in Mice  

PubMed Central

Acute kidney injury (AKI) contributes to the high morbidity and mortality of multi-system organ failure in sepsis. However, recovery of renal function after sepsis-induced AKI suggests active repair of energy-producing pathways. Here, we tested the hypothesis in mice that Staphyloccocus aureus sepsis damages mitochondrial DNA (mtDNA) in the kidney and activates mtDNA repair and mitochondrial biogenesis. Sepsis was induced in wild-type C57Bl/6J and Cox-8 Gfp-tagged mitochondrial-reporter mice via intraperitoneal fibrin clots embedded with S. aureus. Kidneys from surviving mice were harvested at time zero (control), 24, or 48 hours after infection and evaluated for renal inflammation, oxidative stress markers, mtDNA content, and mitochondrial biogenesis markers, and OGG1 and UDG mitochondrial DNA repair enzymes. We examined the kidneys of the mitochondrial reporter mice for changes in staining density and distribution. S. aureus sepsis induced sharp amplification of renal Tnf, Il-10, and Ngal mRNAs with decreased renal mtDNA content and increased tubular and glomerular cell death and accumulation of protein carbonyls and 8-OHdG. Subsequently, mtDNA repair and mitochondrial biogenesis was evidenced by elevated OGG1 levels and significant increases in NRF-1, NRF-2, and mtTFA expression. Overall, renal mitochondrial mass, tracked by citrate synthase mRNA and protein, increased in parallel with changes in mitochondrial GFP-fluorescence especially in proximal tubules in the renal cortex and medulla. Sub-lethal S. aureus sepsis thus induces widespread renal mitochondrial damage that triggers the induction of the renal mtDNA repair protein, OGG1, and mitochondrial biogenesis as a conspicuous resolution mechanism after systemic bacterial infection. PMID:24988481

Bartz, Raquel R.; Fu, Ping; Suliman, Hagir B.; Crowley, Stephen D.; MacGarvey, Nancy Chou; Welty-Wolf, Karen; Piantadosi, Claude A.

2014-01-01

37

Upregulation of Human Selenoprotein H in murine hippocampal neuronal cells promotes mitochondrial biogenesis and functional performance  

PubMed Central

Overexpression of selenoprotein H (SelH) gene provides neuroprotection in neurons against UVB-induced cell death by blocking the mitohcondria-initiated apoptotic cell death pathway. This study examined the effects of SelH on mitochondrial biogenesis and mitochondrial function. The results demonstrated that overexpression of SelH gene in neuronal HT22 cells significantly increased the levels of mitochondrial biogenesis regulators, nuclear respiratory factor-1 (NRF-1), peroxisome proliferator-activated receptor- coactivator-1 alpha (PGC-1?) and mitochondrial transcription factor A (Tfam). Mitochondrial cytochrome c content was elevated, mass was increased and respiration was enhanced. SelH transfection ameliorated ultra violet B (UVB)-induced suppression of mitochondrial biogenesis markers and depolarization of mitochondrial membrane potential. Overexpression of SelH promotes mitochondrial biogenesis and improves mitochondrial functional performance. PMID:20656065

Mendelev, Natalia; Mehta, Suresh L.; Witherspoon, Sam; He, Qingping; Sexton, Jonathan Z.; Li, P. Andy

2010-01-01

38

Selenium preserves mitochondrial function, stimulates mitochondrial biogenesis, and reduces infarct volume after focal cerebral ischemia  

PubMed Central

Background Mitochondrial dysfunction is one of the major events responsible for activation of neuronal cell death pathways during cerebral ischemia. Trace element selenium has been shown to protect neurons in various diseases conditions. Present study is conducted to demonstrate that selenium preserves mitochondrial functional performance, activates mitochondrial biogenesis and prevents hypoxic/ischemic cell damage. Results The study conducted on HT22 cells exposed to glutamate or hypoxia and mice subjected to 60-min focal cerebral ischemia revealed that selenium (100 nM) pretreatment (24?h) significantly attenuated cell death induced by either glutamate toxicity or hypoxia. The protective effects were associated with reduction of glutamate and hypoxia-induced ROS production and alleviation of hypoxia-induced suppression of mitochondrial respiratory complex activities. The animal studies demonstrated that selenite pretreatment (0.2?mg/kg?i.p. once a day for 7?days) ameliorated cerebral infarct volume and reduced DNA oxidation. Furthermore, selenite increased protein levels of peroxisome proliferator-activated receptor-? coactivator 1alpha (PGC-1?) and nuclear respiratory factor 1 (NRF1), two key nuclear factors that regulate mitochondrial biogenesis. Finally, selenite normalized the ischemia-induced activation of Beclin 1 and microtubule-associated protein 1 light chain 3-II (LC3-II), markers for autophagy. Conclusions These results suggest that selenium protects neurons against hypoxic/ischemic damage by reducing oxidative stress, restoring mitochondrial functional activities and stimulating mitochondrial biogenesis. PMID:22776356

2012-01-01

39

Lipophilic antioxidants prevent lipopolysaccharide-induced mitochondrial dysfunction through mitochondrial biogenesis improvement.  

PubMed

Oxidative stress is implicated in several infectious diseases. In this regard, lipopolysaccharide (LPS), an endotoxic component, induces mitochondrial dysfunction and oxidative stress in several pathological events such as periodontal disease or sepsis. In our experiments, LPS-treated fibroblasts provoked increased oxidative stress, mitochondrial dysfunction, reduced oxygen consumption and mitochondrial biogenesis. After comparing coenzyme Q10 (CoQ10) and N-acetylcysteine (NAC), we observed a more significant protection of CoQ10 than of NAC, which was comparable with other lipophilic and hydrophilic antioxidants such as vitamin E or BHA respectively. CoQ10 improved mitochondrial biogenesis by activating PGC-1? and TFAM. This lipophilic antioxidant protection was observed in mice after LPS injection. These results show that mitochondria-targeted lipophilic antioxidants could be a possible specific therapeutic strategy in pharmacology in the treatment of infectious diseases and their complications. PMID:25447593

Bullón, Pedro; Román-Malo, Lourdes; Marín-Aguilar, Fabiola; Alvarez-Suarez, José Miguel; Giampieri, Francesca; Battino, Maurizio; Cordero, Mario D

2015-01-01

40

Animal mitochondrial biogenesis and function: a regulatory cross-talk between two genomes  

Microsoft Academic Search

Mitochondria play a pivotal role in cell physiology, producing the cellular energy and other essential metabolites as well as controlling apoptosis by integrating numerous death signals. The biogenesis of the oxidative phosphorylation system (OXPHOS) depends on the coordinated expression of two genomes, nuclear and mitochondrial. As a consequence, the control of mitochondrial biogenesis and function depends on extremely complex processes

Rafael Garesse; Carmen G. Vallejo

2001-01-01

41

Mitochondrial biogenesis in the pulmonary vasculature during inhalation lung injury and fibrosis  

EPA Science Inventory

Cell survival and injury repair is facilitated by mitochondrial biogenesis; however, the role of this process in lung repair is unknown. We evaluated mitochondrial biogenesis in the mouse lung in two injuries that cause acute inflammation and in two that cause chronic inflammatio...

42

MITOCHONDRIAL BIOGENESIS DURING DIFFERENTIATION OF ARTEMIA SALINA CYSTS  

PubMed Central

Mitochondria isolated from cysts of Artemia salina (brine shrimp) were found to be devoid of cristae and to possess a low respiratory capability. Hydration of the cysts induces marked biochemical and morphological changes in the mitochondria. Their biogenesis proceeds in two stages. The first stage is completed within 1 h and is characterized by a rapid increase in the respiratory capability of the mitochondria, their cytochrome oxidase, cytochrome b, cytochrome c and perhaps some morphological changes. In the second stage there is an increase in the protein-synthesizing capacity of the mitochondria as well as striking changes in mitochondrial morphology leading to the formation of cristae. PMID:4355924

Schmitt, H.; Grossfeld, H.; Littauer, U. Z.

1973-01-01

43

MTERF3 Regulates Mitochondrial Ribosome Biogenesis in Invertebrates and Mammals  

PubMed Central

Regulation of mitochondrial DNA (mtDNA) expression is critical for the control of oxidative phosphorylation in response to physiological demand, and this regulation is often impaired in disease and aging. We have previously shown that mitochondrial transcription termination factor 3 (MTERF3) is a key regulator that represses mtDNA transcription in the mouse, but its molecular mode of action has remained elusive. Based on the hypothesis that key regulatory mechanisms for mtDNA expression are conserved in metazoans, we analyzed Mterf3 knockout and knockdown flies. We demonstrate here that decreased expression of MTERF3 not only leads to activation of mtDNA transcription, but also impairs assembly of the large mitochondrial ribosomal subunit. This novel function of MTERF3 in mitochondrial ribosomal biogenesis is conserved in the mouse, thus we identify a novel and unexpected role for MTERF3 in coordinating the crosstalk between transcription and translation for the regulation of mammalian mtDNA gene expression. PMID:23300484

Metodiev, Metodi D.; Spåhr, Henrik; Mourier, Arnaud; Freyer, Christoph; Ruzzenente, Benedetta; Tain, Luke; Grönke, Sebastian; Baggio, Francesca; Kukat, Christian; Kremmer, Elisabeth; Wibom, Rolf; Polosa, Paola Loguercio; Habermann, Bianca; Partridge, Linda; Park, Chan Bae; Larsson, Nils-Göran

2013-01-01

44

Regulation of Mitochondrial Biogenesis in Skeletal Muscle by CaMK  

Microsoft Academic Search

Endurance exercise training promotes mitochondrial biogenesis in skeletal muscle and enhances muscle oxidative capacity, but the signaling mechanisms involved are poorly understood. To investigate this adaptive process, we generated transgenic mice that selectively express in skeletal muscle a constitutively active form of calcium\\/calmodulin-dependent protein kinase IV (CaMKIV*). Skeletal muscles from these mice showed augmented mitochondrial DNA replication and mitochondrial biogenesis,

Hai Wu; Shane B. Kanatous; Frederick A. Thurmond; Teresa Gallardo; Eiji Isotani; Rhonda Bassel-Duby; R. Sanders Williams

2002-01-01

45

The ?2-adrenoceptor agonist formoterol stimulates mitochondrial biogenesis.  

PubMed

Mitochondrial dysfunction is a common mediator of disease and organ injury. Although recent studies show that inducing mitochondrial biogenesis (MB) stimulates cell repair and regeneration, only a limited number of chemicals are known to induce MB. To examine the impact of the ?-adrenoceptor (?-AR) signaling pathway on MB, primary renal proximal tubule cells (RPTC) and adult feline cardiomyocytes were exposed for 24 h to multiple ?-AR agonists: isoproterenol (nonselective ?-AR agonist), (±)-(R*,R*)-[4-[2-[[2-(3-chlorophenyl)-2-hydroxyethyl]amino]propyl]phenoxy] acetic acid sodium hydrate (BRL 37344) (selective ?(3)-AR agonist), and formoterol (selective ?(2)-AR agonist). The Seahorse Biosciences (North Billerica, MA) extracellular flux analyzer was used to quantify carbonylcyanide p-trifluoromethoxyphenylhydrazone (FCCP)-uncoupled oxygen consumption rate (OCR), a marker of maximal electron transport chain activity. Isoproterenol and BRL 37244 did not alter mitochondrial respiration at any of the concentrations examined. Formoterol exposure resulted in increases in both FCCP-uncoupled OCR and mitochondrial DNA (mtDNA) copy number. The effect of formoterol on OCR in RPTC was inhibited by the ?-AR antagonist propranolol and the ?(2)-AR inverse agonist 3-(isopropylamino)-1-[(7-methyl-4-indanyl)oxy]butan-2-ol hydrochloride (ICI-118,551). Mice exposed to formoterol for 24 or 72 h exhibited increases in kidney and heart mtDNA copy number, peroxisome proliferator-activated receptor ? coactivator 1?, and multiple genes involved in the mitochondrial electron transport chain (F0 subunit 6 of transmembrane F-type ATP synthase, NADH dehydrogenase subunit 1, NADH dehydrogenase subunit 6, and NADH dehydrogenase [ubiquinone] 1? subcomplex subunit 8). Cheminformatic modeling, virtual chemical library screening, and experimental validation identified nisoxetine from the Sigma Library of Pharmacologically Active Compounds and two compounds from the ChemBridge DIVERSet that increased mitochondrial respiratory capacity. These data provide compelling evidence for the use and development of ?(2)-AR ligands for therapeutic MB. PMID:22490378

Wills, Lauren P; Trager, Richard E; Beeson, Gyda C; Lindsey, Christopher C; Peterson, Yuri K; Beeson, Craig C; Schnellmann, Rick G

2012-07-01

46

Sirt3 Protects Cortical Neurons against Oxidative Stress via Regulating Mitochondrial Ca2+ and Mitochondrial Biogenesis  

PubMed Central

Oxidative stress is a well-established event in the pathology of several neurobiological diseases. Sirt3 is a nicotinamide adenine nucleotide (NAD+)-dependent protein deacetylase that regulates mitochondrial function and metabolism in response to caloric restriction and stress. This study aims to investigate the role of Sirt3 in H2O2 induced oxidative neuronal injury in primary cultured rat cortical neurons. We found that H2O2 treatment significantly increased the expression of Sirt3 in a time-dependent manner at both mRNA and protein levels. Knockdown of Sirt3 with a specific small interfering RNA (siRNA) exacerbated H2O2-induced neuronal injury, whereas overexpression of Sirt3 by lentivirus transfection inhibited H2O2-induced neuronal damage reduced the generation of reactive oxygen species (ROS), and increased the activities of endogenous antioxidant enzymes. In addition, the intra-mitochondrial Ca2+ overload, but not cytosolic Ca2+ increase after H2O2 treatment, was strongly attenuated after Sirt3 overexpression. Overexpression of Sirt3 also increased the content of mitochondrial DNA (mtDNA) and the expression of mitochondrial biogenesis related transcription factors. All these results suggest that Sirt3 acts as a prosurvival factor playing an essential role to protect cortical neurons under H2O2 induced oxidative stress, possibly through regulating mitochondrial Ca2+ homeostasis and mitochondrial biogenesis. PMID:25196599

Dai, Shu-Hui; Chen, Tao; Wang, Yu-Hai; Zhu, Jie; Luo, Peng; Rao, Wei; Yang, Yue-Fan; Fei, Zhou; Jiang, Xiao-Fan

2014-01-01

47

Sirt3 protects cortical neurons against oxidative stress via regulating mitochondrial Ca2+ and mitochondrial biogenesis.  

PubMed

Oxidative stress is a well-established event in the pathology of several neurobiological diseases. Sirt3 is a nicotinamide adenine nucleotide (NAD+)-dependent protein deacetylase that regulates mitochondrial function and metabolism in response to caloric restriction and stress. This study aims to investigate the role of Sirt3 in H2O2 induced oxidative neuronal injury in primary cultured rat cortical neurons. We found that H2O2 treatment significantly increased the expression of Sirt3 in a time-dependent manner at both mRNA and protein levels. Knockdown of Sirt3 with a specific small interfering RNA (siRNA) exacerbated H2O2-induced neuronal injury, whereas overexpression of Sirt3 by lentivirus transfection inhibited H2O2-induced neuronal damage reduced the generation of reactive oxygen species (ROS), and increased the activities of endogenous antioxidant enzymes. In addition, the intra-mitochondrial Ca2+ overload, but not cytosolic Ca2+ increase after H2O2 treatment, was strongly attenuated after Sirt3 overexpression. Overexpression of Sirt3 also increased the content of mitochondrial DNA (mtDNA) and the expression of mitochondrial biogenesis related transcription factors. All these results suggest that Sirt3 acts as a prosurvival factor playing an essential role to protect cortical neurons under H2O2 induced oxidative stress, possibly through regulating mitochondrial Ca2+ homeostasis and mitochondrial biogenesis. PMID:25196599

Dai, Shu-Hui; Chen, Tao; Wang, Yu-Hai; Zhu, Jie; Luo, Peng; Rao, Wei; Yang, Yue-Fan; Fei, Zhou; Jiang, Xiao-Fan

2014-01-01

48

The effect of ethidium bromide and chloramphenicol on mitochondrial biogenesis in primary human fibroblasts  

SciTech Connect

The expression of mitochondrial components is controlled by an intricate interplay between nuclear transcription factors and retrograde signaling from mitochondria. The role of mitochondrial DNA (mtDNA) and mtDNA-encoded proteins in mitochondrial biogenesis is, however, poorly understood and thus far has mainly been studied in transformed cell lines. We treated primary human fibroblasts with ethidium bromide (EtBr) or chloramphenicol for six weeks to inhibit mtDNA replication or mitochondrial protein synthesis, respectively, and investigated how the cells recovered from these insults two weeks after removal of the drugs. Although cellular growth and mitochondrial gene expression were severely impaired after both inhibitor treatments we observed marked differences in mitochondrial structure, membrane potential, glycolysis, gene expression, and redox status between fibroblasts treated with EtBr and chloramphenicol. Following removal of the drugs we further detected clear differences in expression of both mtDNA-encoded genes and nuclear transcription factors that control mitochondrial biogenesis, suggesting that the cells possess different compensatory mechanisms to recover from drug-induced mitochondrial dysfunction. Our data reveal new aspects of the interplay between mitochondrial retrograde signaling and the expression of nuclear regulators of mitochondrial biogenesis, a process with direct relevance to mitochondrial diseases and chloramphenicol toxicity in humans. -- Highlights: ? Cells respond to certain environmental toxins by increasing mitochondrial biogenesis. ? We investigated the effect of Chloramphenicol and EtBr in primary human fibroblasts. ? Inhibiting mitochondrial protein synthesis or DNA replication elicit different effects. ? We provide novel insights into the cellular responses toxins and antibiotics.

Kao, Li-Pin; Ovchinnikov, Dmitry; Wolvetang, Ernst, E-mail: e.wolvetang@uq.edu.au

2012-05-15

49

AMP kinase is required for mitochondrial biogenesis in skeletal muscle in response to chronic energy deprivation  

Microsoft Academic Search

Mitochondrial biogenesis is a critical adaptation to chronic energy deprivation, yet the signaling mechanisms responsible for this response are poorly understood. To examine the role of AMP-activated protein kinase (AMPK), an evolutionarily conserved fuel sensor, in mitochondrial biogenesis we studied transgenic mice expressing a dominant-negative mutant of AMPK in muscle (DN-AMPK). Both DN-AMPK and WT mice were treated with -guanidinopropionic

Haihong Zong; Jian Ming Ren; Lawrence H. Young; Marc Pypaert; James Mu; Morris J. Birnbaum; Gerald I. Shulman

2002-01-01

50

Delphinidin inhibits VEGF induced-mitochondrial biogenesis and Akt activation in endothelial cells.  

PubMed

Delphinidin, an anthocyanin present in red wine, has been reported to exert vasculoprotective properties on endothelial cells, including vasorelaxing and anti-apoptotic effects. Moreover, delphinidin treatment in a rat model of post-ischemic neovascularization has been described to exert anti-angiogenic property. Angiogenesis is an energetic process and VEGF-induced angiogenesis is associated with mitochondrial biogenesis. However, whether delphinidin induces changes in mitochondrial biogenesis has never been addressed. Effects of delphinidin were investigated in human endothelial cells at a concentration described to be anti-angiogenic in vitro (10(-2)g/l). mRNA expression of mitochondrial biogenesis factors, mitochondrial respiration, DNA content and enzyme activities were assessed after 48 h of stimulation. Delphinidin increased mRNA expression of several mitochondrial biogenesis factors, including NRF1, ERR?, Tfam, Tfb2m and PolG but did not affect neither mitochondrial respiration, DNA content nor enzyme activities. In presence of delphinidin, VEGF failed to increase mitochondrial respiration, DNA content, complex IV activity and Akt activation in endothelial cells. These results suggest a possible association between inhibition of VEGF-induced mitochondrial biogenesis through Akt pathway by delphinidin and its anti-angiogenic effect, providing a novel mechanism sustaining the beneficial effect of delphinidin against pathologies associated with excessive angiogenesis such as cancers. PMID:24792670

Duluc, Lucie; Jacques, Caroline; Soleti, Raffaella; Andriantsitohaina, Ramaroson; Simard, Gilles

2014-08-01

51

Oxidative Stress and Upregulation of Mitochondrial Biogenesis Genes in Mitochondrial DNA-Depleted HeLa Cells  

Microsoft Academic Search

The signaling mechanism through which deficitary mitochondrial function would activate nuclear genes required for mitochondrial biogenesis, has not been established. To explore the hypothesis that reactive oxygen species (ROS), a mitochondrial product, constitute part of the mitochondria-nuclei signaling pathway, we obtained HeLa cells depleted of mitochondrial DNA (?0cells) through exposure to ethidium bromide. We found evidences of oxidative stress in

Soledad Miranda; Rocio Foncea; Javier Guerrero; Federico Leighton

1999-01-01

52

Mitochondrial Rab GAPs govern autophagosome biogenesis during mitophagy  

PubMed Central

Damaged mitochondria can be selectively eliminated by mitophagy. Although two gene products mutated in Parkinson’s disease, PINK1, and Parkin have been found to play a central role in triggering mitophagy in mammals, how the pre-autophagosomal isolation membrane selectively and accurately engulfs damaged mitochondria remains unclear. In this study, we demonstrate that TBC1D15, a mitochondrial Rab GTPase-activating protein (Rab-GAP), governs autophagosome biogenesis and morphology downstream of Parkin activation. To constrain autophagosome morphogenesis to that of the cargo, TBC1D15 inhibits Rab7 activity and associates with both the mitochondria through binding Fis1 and the isolation membrane through the interactions with LC3/GABARAP family members. Another TBC family member TBC1D17, also participates in mitophagy and forms homodimers and heterodimers with TBC1D15. These results demonstrate that TBC1D15 and TBC1D17 mediate proper autophagic encapsulation of mitochondria by regulating Rab7 activity at the interface between mitochondria and isolation membranes. DOI: http://dx.doi.org/10.7554/eLife.01612.001 PMID:24569479

Yamano, Koji; Fogel, Adam I; Wang, Chunxin; van der Bliek, Alexander M; Youle, Richard J

2014-01-01

53

Mitochondrial Rab GAPs govern autophagosome biogenesis during mitophagy.  

PubMed

Damaged mitochondria can be selectively eliminated by mitophagy. Although two gene products mutated in Parkinson's disease, PINK1, and Parkin have been found to play a central role in triggering mitophagy in mammals, how the pre-autophagosomal isolation membrane selectively and accurately engulfs damaged mitochondria remains unclear. In this study, we demonstrate that TBC1D15, a mitochondrial Rab GTPase-activating protein (Rab-GAP), governs autophagosome biogenesis and morphology downstream of Parkin activation. To constrain autophagosome morphogenesis to that of the cargo, TBC1D15 inhibits Rab7 activity and associates with both the mitochondria through binding Fis1 and the isolation membrane through the interactions with LC3/GABARAP family members. Another TBC family member TBC1D17, also participates in mitophagy and forms homodimers and heterodimers with TBC1D15. These results demonstrate that TBC1D15 and TBC1D17 mediate proper autophagic encapsulation of mitochondria by regulating Rab7 activity at the interface between mitochondria and isolation membranes. DOI: http://dx.doi.org/10.7554/eLife.01612.001. PMID:24569479

Yamano, Koji; Fogel, Adam I; Wang, Chunxin; van der Bliek, Alexander M; Youle, Richard J

2014-01-01

54

Coordinated changes in mitochondrial function and biogenesis in healthy and diseased human skeletal muscle  

Microsoft Academic Search

We examined the transcriptional signal- ing cascade involved in the changes of mitochondrial biogenesis and mitochondrial function of skeletal mus- cle and of the exercise capacity of humans in response to long-term physical activity and chronic heart failure (CHF). Biopsy samples of vastus lateralis muscle were obtained from 18 healthy subjects with different fitness levels (assessed by maximal oxygen uptake,

Anne Garnier; Dominique Fortin; Joffrey Zoll; Benoit N'Guessan; Bertrand Mettauer; Eliane Lampert; Vladimir Veksler; Renee Ventura-Clapier

2005-01-01

55

The effects of NAD+ on apoptotic neuronal death and mitochondrial biogenesis and function after glutamate excitotoxicity.  

PubMed

NAD+ is an essential co-enzyme for cellular energy metabolism and is also involved as a substrate for many cellular enzymatic reactions. It has been shown that NAD+ has a beneficial effect on neuronal survival and brain injury in in vitro and in vivo ischemic models. However, the effect of NAD+ on mitochondrial biogenesis and function in ischemia has not been well investigated. In the present study, we used an in vitro glutamate excitotoxicity model of primary cultured cortical neurons to study the effect of NAD+ on apoptotic neuronal death and mitochondrial biogenesis and function. Our results show that supplementation of NAD+ could effectively reduce apoptotic neuronal death, and apoptotic inducing factor translocation after neurons were challenged with excitotoxic glutamate stimulation. Using different approaches including confocal imaging, mitochondrial DNA measurement and Western blot analysis of PGC-1 and NRF-1, we also found that NAD+ could significantly attenuate glutamate-induced mitochondrial fragmentation and the impairment of mitochondrial biogenesis. Furthermore, NAD+ treatment effectively inhibited mitochondrial membrane potential depolarization and NADH redistribution after excitotoxic glutamate stimulation. Taken together, our results demonstrated that NAD+ is capable of inhibiting apoptotic neuronal death after glutamate excitotoxicity via preserving mitochondrial biogenesis and integrity. Our findings provide insights into potential neuroprotective strategies in ischemic stroke. PMID:25387075

Wang, Xiaowan; Li, Hailong; Ding, Shinghua

2014-01-01

56

Peroxynitrite induced mitochondrial biogenesis following MnSOD knockdown in normal rat kidney (NRK) cells.  

PubMed

Superoxide is widely regarded as the primary reactive oxygen species (ROS) which initiates downstream oxidative stress. Increased oxidative stress contributes, in part, to many disease conditions such as cancer, atherosclerosis, ischemia/reperfusion, diabetes, aging, and neurodegeneration. Manganese superoxide dismutase (MnSOD) catalyzes the dismutation of superoxide into hydrogen peroxide which can then be further detoxified by other antioxidant enzymes. MnSOD is critical in maintaining the normal function of mitochondria, thus its inactivation is thought to lead to compromised mitochondria. Previously, our laboratory observed increased mitochondrial biogenesis in a novel kidney-specific MnSOD knockout mouse. The current study used transient siRNA mediated MnSOD knockdown of normal rat kidney (NRK) cells as the in vitro model, and confirmed functional mitochondrial biogenesis evidenced by increased PGC1? expression, mitochondrial DNA copy numbers and integrity, electron transport chain protein CORE II, mitochondrial mass, oxygen consumption rate, and overall ATP production. Further mechanistic studies using mitoquinone (MitoQ), a mitochondria-targeted antioxidant and L-NAME, a nitric oxide synthase (NOS) inhibitor demonstrated that peroxynitrite (at low micromolar levels) induced mitochondrial biogenesis. These findings provide the first evidence that low levels of peroxynitrite can initiate a protective signaling cascade involving mitochondrial biogenesis which may help to restore mitochondrial function following transient MnSOD inactivation. PMID:24563852

Marine, Akira; Krager, Kimberly J; Aykin-Burns, Nukhet; Macmillan-Crow, Lee Ann

2014-01-01

57

Reactive oxygen species mediates homocysteine-induced mitochondrial biogenesis in human endothelial cells: Modulation by antioxidants  

SciTech Connect

It has been proposed that homocysteine (Hcy)-induces endothelial dysfunction and atherosclerosis by generation of reactive oxygen species (ROS). A previous report has shown that Hcy promotes mitochondrial damage. Considering that oxidative stress can affect mitochondrial biogenesis, we hypothesized that Hcy-induced ROS in endothelial cells may lead to increased mitochondrial biogenesis. We found that Hcy-induced ROS (1.85-fold), leading to a NF-{kappa}B activation and increase the formation of 3-nitrotyrosine. Furthermore, expression of the mitochondrial biogenesis factors, nuclear respiratory factor-1 and mitochondrial transcription factor A, was significantly elevated in Hcy-treated cells. These changes were accompanied by increase in mitochondrial mass and higher mRNA and protein expression of the subunit III of cytochrome c oxidase. These effects were significantly prevented by pretreatment with the antioxidants, catechin and trolox. Taken together, our results suggest that ROS is an important mediator of mitochondrial biogenesis induced by Hcy, and that modulation of oxidative stress by antioxidants may protect against the adverse vascular effects of Hcy.

Perez-de-Arce, Karen [Departamento de Nutricion, Diabetes y Metabolismo, Facultad de Medicina, Pontificia Universidad Catolica de Chile, Santiago (Chile); Departamento de Biologia Celular y Molecular, Facultad de Ciencias Biologicas, Pontificia Universidad Catolica de Chile, Santiago (Chile); Foncea, Rocio [Departamento de Nutricion, Diabetes y Metabolismo, Facultad de Medicina, Pontificia Universidad Catolica de Chile, Santiago (Chile)]. E-mail: rfoncea@med.puc.cl; Leighton, Federico [Departamento de Biologia Celular y Molecular, Facultad de Ciencias Biologicas, Pontificia Universidad Catolica de Chile, Santiago (Chile)

2005-12-16

58

Mechanisms Controlling Mitochondrial Biogenesis and Respiration through the Thermogenic Coactivator PGC1  

Microsoft Academic Search

Mitochondrial number and function are altered in response to external stimuli in eukaryotes. While several transcription\\/replication factors directly regulate mitochondrial genes, the coordination of these factors into a program responsive to the environment is not understood. We show here that PGC-1, a cold-inducible coactivator of nuclear receptors, stimulates mitochondrial biogenesis and respiration in muscle cells through an induction of uncoupling

Zhidan Wu; Pere Puigserver; Ulf Andersson; Chenyu Zhang; Guillaume Adelmant; Vamsi Mootha; Amy Troy; Saverio Cinti; Bradford Lowell; Richard C. Scarpulla; Bruce M. Spiegelman

1999-01-01

59

Mitochondrial Biogenesis in the Liver during Development and Oncogenesis  

Microsoft Academic Search

The analysis of the expression of oxidative phosphorylation genes in the liver during development reveals the existence of two biological programs involved in the biogenesis of mitochondria. Differentiation is a short-term program of biogenesis that is controlled at post-transcriptional levels of gene expression and is responsible for the rapid changes in the bioenergetic phenotype of mitochondria. In contrast, proliferation is

José M. Cuezva; Luciana K. Ostronoff; Javier Ricart; Miguel López de Heredia; Carlo M. Di Liegro; José M. Izquierdo

1997-01-01

60

Nitrite Activates AMP Kinase to Stimulate Mitochondrial Biogenesis Independent of soluble Guanylate Cyclase  

PubMed Central

Nitrite, a dietary constituent and endogenous signaling molecule, mediates a number of physiological responses including modulation of ischemia/reperfusion injury, glucose tolerance and vascular remodeling. While the exact molecular mechanisms underlying nitrite’s actions are unknown, current paradigm suggests that these effects depend on the hypoxic reduction of nitrite to nitric oxide (NO). Mitochondrial biogenesis is a fundamental mechanism of cellular adaptation and repair. However, the effect of nitrite on mitochondrial number has not been explored. Herein, we report that nitrite stimulates mitochondrial biogenesis through a mechanism distinct from NO. We demonstrate that nitrite significantly increases cellular mitochondrial number by augmenting the activity of adenylate kinase, resulting in AMP kinase phosphorylation, downstream activation of sirtuin-1, and de-acetylation of PGC1, the master regulator of mitochondrial biogenesis. Unlike NO, nitrite-mediated biogenesis does not require the activation of soluble guanylate cyclase and results in the synthesis of more functionally efficient mitochondria. Further, we provide evidence that nitrite mediates biogenesis in vivo. In a rat model of carotid injury, two weeks of continuous oral nitrite treatment post-injury prevents the hyperproliferative response of smooth muscle cells. This protection is accompanied by a nitrite-dependent upregulation of PGC1 and increased mitochondrial number in the injured artery. These data are the first to demonstrate that nitrite mediates differential signaling than NO. They show that nitrite is a versatile regulator of mitochondrial function and number both in vivo and in vitro, and suggest that nitrite-mediated biogenesis may play a protective role in the setting of vascular injury. PMID:22892143

Mo, Li; Wang, Yinna; Geary, Lisa; Corey, Catherine; Alef, Matthew J.; Beer-Stolz, Donna; Zuckerbraun, Brian S.; Shiva, Sruti

2012-01-01

61

Exercise-Mediated Wall Shear Stress Increases Mitochondrial Biogenesis in Vascular Endothelium  

PubMed Central

Objective Enhancing structural and functional integrity of mitochondria is an emerging therapeutic option against endothelial dysfunction. In this study, we sought to investigate the effect of fluid shear stress on mitochondrial biogenesis and mitochondrial respiratory function in endothelial cells (ECs) using in vitro and in vivo complementary studies. Methods and Results Human aortic- or umbilical vein-derived ECs were exposed to laminar shear stress (20 dyne/cm2) for various durations using a cone-and-plate shear apparatus. We observed significant increases in the expression of key genes related to mitochondrial biogenesis and mitochondrial quality control as well as mtDNA content and mitochondrial mass under the shear stress conditions. Mitochondrial respiratory function was enhanced when cells were intermittently exposed to laminar shear stress for 72 hrs. Also, shear-exposed cells showed diminished glycolysis and decreased mitochondrial membrane potential (??m). Likewise, in in vivo experiments, mice that were subjected to a voluntary wheel running exercise for 5 weeks showed significantly higher mitochondrial content determined by en face staining in the conduit (greater and lesser curvature of the aortic arch and thoracic aorta) and muscle feed (femoral artery) arteries compared to the sedentary control mice. Interestingly, however, the mitochondrial biogenesis was not observed in the mesenteric artery. This region-specific adaptation is likely due to the differential blood flow redistribution during exercise in the different vessel beds. Conclusion Taken together, our findings suggest that exercise enhances mitochondrial biogenesis in vascular endothelium through a shear stress-dependent mechanism. Our findings may suggest a novel mitochondrial pathway by which a chronic exercise may be beneficial for vascular function. PMID:25375175

Kim, Boa; Lee, Hojun; Kawata, Keisuke; Park, Joon-Young

2014-01-01

62

Stomatin-Like Protein 2 Binds Cardiolipin and Regulates Mitochondrial Biogenesis and Function?  

PubMed Central

Stomatin-like protein 2 (SLP-2) is a widely expressed mitochondrial inner membrane protein of unknown function. Here we show that human SLP-2 interacts with prohibitin-1 and -2 and binds to the mitochondrial membrane phospholipid cardiolipin. Upregulation of SLP-2 expression increases cardiolipin content and the formation of metabolically active mitochondrial membranes and induces mitochondrial biogenesis. In human T lymphocytes, these events correlate with increased complex I and II activities, increased intracellular ATP stores, and increased resistance to apoptosis through the intrinsic pathway, ultimately enhancing cellular responses. We propose that the function of SLP-2 is to recruit prohibitins to cardiolipin to form cardiolipin-enriched microdomains in which electron transport complexes are optimally assembled. Likely through the prohibitin functional interactome, SLP-2 then regulates mitochondrial biogenesis and function. PMID:21746876

Christie, Darah A.; Lemke, Caitlin D.; Elias, Isaac M.; Chau, Luan A.; Kirchhof, Mark G.; Li, Bo; Ball, Eric H.; Dunn, Stanley D.; Hatch, Grant M.; Madrenas, Joaquín

2011-01-01

63

Mitochondrial cardiolipin involved in outer membrane protein biogenesis: implications for Barth syndrome  

PubMed Central

Summary The biogenesis of mitochondria requires the import of a large number of proteins from the cytosol [1, 2]. While numerous studies have defined the proteinaceous machineries that mediate mitochondrial protein sorting, little is known about the role of lipids in mitochondrial protein import. Cardiolipin, the signature phospholipid of the mitochondrial inner membrane [3–5], affects the stability of many inner membrane protein complexes [6–12]. Perturbation of cardiolipin metabolism leads to the X-linked cardioskeletal myopathy, Barth syndrome [13–18]. We report that cardiolipin affects the preprotein translocases of the mitochondrial outer membrane. Cardiolipin mutants genetically interact with mutants of outer membrane translocases. Mitochondria from cardiolipin yeast mutants, as well as Barth syndrome patients, are impaired in the biogenesis of outer membrane proteins. Our findings reveal a new role for cardiolipin in protein sorting at the mitochondrial outer membrane and bear implications for the pathogenesis of Barth syndrome. PMID:19962311

Gebert, Natalia; Joshi, Amit S.; Kutik, Stephan; Becker, Thomas; McKenzie, Matthew; Guan, Xue Li; Mooga, Ved P.; Stroud, David A.; Kulkarni, Gnanada; Wenk, Markus R.; Rehling, Peter; Meisinger, Chris; Ryan, Michael T.; Wiedemann, Nils; Greenberg, Miriam L.; Pfanner, Nikolaus

2009-01-01

64

Complementary RNA and Protein Profiling Identifies Iron as a Key Regulator of Mitochondrial Biogenesis  

PubMed Central

Summary Mitochondria are centers of metabolism and signaling whose content and function must adapt to changing cellular environments. The biological signals that initiate mitochondrial restructuring and the cellular processes that drive this adaptive response are largely obscure. To better define these systems, we performed matched quantitative genomic and proteomic analyses of mouse muscle cells as they performed mitochondrial biogenesis. We find that proteins involved in cellular iron homeostasis are highly coordinated with this process and that depletion of cellular iron results in a rapid, dose-dependent decrease of select mitochondrial protein levels and oxidative capacity. We further show that this process is universal across a broad range of cell types and fully reversed when iron is reintroduced. Collectively, our work reveals that cellular iron is a key regulator of mitochondrial biogenesis, and provides quantitative data sets that can be leveraged to explore posttranscriptional and posttranslational processes that are essential for mitochondrial adaptation. PMID:23318259

Rensvold, Jarred W.; Ong, Shao-En; Jeevananthan, Athavi; Carr, Steven A.; Mootha, Vamsi K.; Pagliarini, David J.

2013-01-01

65

Jac1, a mitochondrial J-type chaperone, is involved in the biogenesis of Fe S clusters in  

E-print Network

Jac1, a mitochondrial J-type chaperone, is involved in the biogenesis of Fe S clusters, Poland Contributed by Elizabeth A. Craig, November 28, 2000 A minor Hsp70 chaperone of the mitochondrial and or mitochondrial iron metabolism. Here, we report evidence that Jac1, a J-type chaperone of the mitochondrial

Craig, Elizabeth A

66

Transcriptional Control of Mitochondrial Biogenesis and Its Interface with Inflammatory Processes  

PubMed Central

Background Cells avoid major mitochondrial damage and energy failure during systemic inflammatory states, such as severe acute infections, by specific targeting of the inflammatory response and by inducing anti-inflammatory and anti-oxidant defenses. Recent evidence indicates that these cell defenses also include mitochondrial biogenesis and the clearance of damaged mitochondria through autophagy. Scope of Review This review addresses a group of transcriptional signaling mechanisms that engage mitochondrial biogenesis, including energy-sensing and redox-regulated transcription factors and co-activators, after major inflammatory events. Major Conclusions Stimulation of the innate immune system by activation of toll-like receptors (TLR) generates pro-inflammatory mediators, such as tumor necrosis factor-? (TNF-?) and interleukin-1?, (IL-1?), necessary for optimal host defense, but which also contribute to mitochondrial damage through oxidative stress and other mechanisms. To protect its energy supply, host cells sense mitochondrial damage and initiate mitochondrial biogenesis under the control of an inducible transcriptional program that also activates anti-oxidant and anti-inflammatory gene expression. This multifunctional network not only increases cellular resistance to metabolic failure, oxidative stress, and cell death, but promotes immune tolerance as shown in the graphical abstract. General Significance The post-inflammatory induction of mitochondrial biogenesis supports metabolic function and cell viability while helping to control inflammation. In clinical settings, patients recovering from severe systemic infections may develop transient immune suppression, placing them at risk for recurrent infection, but there may be therapeutic opportunities to enhance mitochondrial quality control that would improve the resolution of life-threatening host responses to such infections. PMID:22265687

Piantadosi, Claude A.; Suliman, Hagir B.

2012-01-01

67

Heterogeneity of Mitochondrial Protein Biogenesis during Primary Leaf Development in Barley  

Microsoft Academic Search

The natural developmental gradient of light-grown primary leaves of barley (Hordeum vulgare L.) was used to analyze the biogenesis of mitochondrial proteins in relation to the age and physiological changes within the leaf. The data indicate that the protein composition of mitochondria changes markedly during leaf development. Three distinct patterns of protein development were noted: group A proteins, consisting of

Peter Thompson; Caroline G. Bowsher; Alyson K. Tobin

1998-01-01

68

Mitochondrial Biogenesis: Cell-Cycle-Dependent Investment in Making Mitochondria.  

PubMed

Mitochondria cannot be made de novo, so pre-existing mitochondria must be inherited at each cell division. A new study demonstrates cell-cycle-dependent regulation of the activity of the TOM translocase complex to induce mitochondrial biogenesis during the M phase of the cell cycle. PMID:25602310

Shiota, Takuya; Traven, Ana; Lithgow, Trevor

2015-01-19

69

Short Term Exercise Induces PGC-1?, Ameliorates Inflammation and Increases Mitochondrial Membrane Proteins but Fails to Increase Respiratory Enzymes in Aging Diabetic Hearts  

PubMed Central

PGC-1?, a transcriptional coactivator, controls inflammation and mitochondrial gene expression in insulin-sensitive tissues following exercise intervention. However, attributing such effects to PGC-1? is counfounded by exercise-induced fluctuations in blood glucose, insulin or bodyweight in diabetic patients. The goal of this study was to investigate the role of PGC-1? on inflammation and mitochondrial protein expressions in aging db/db mice hearts, independent of changes in glycemic parameters. In 8-month-old db/db mice hearts with diabetes lasting over 22 weeks, short-term, moderate-intensity exercise upregulated PGC-1? without altering body weight or glycemic parameters. Nonetheless, such a regimen lowered both cardiac (macrophage infiltration, iNOS and TNF?) and systemic (circulating chemokines and cytokines) inflammation. Curiously, such an anti-inflammatory effect was also linked to attenuated expression of downstream transcription factors of PGC-1? such as NRF-1 and several respiratory genes. Such mismatch between PGC-1? and its downstream targets was associated with elevated mitochondrial membrane proteins like Tom70 but a concurrent reduction in oxidative phosphorylation protein expressions in exercised db/db hearts. As mitochondrial oxidative stress was predominant in these hearts, in support of our in vivo data, increasing concentrations of H2O2 dose-dependently increased PGC-1? expression while inhibiting expression of inflammatory genes and downstream transcription factors in H9c2 cardiomyocytes in vitro. We conclude that short-term exercise-induced oxidative stress may be key in attenuating cardiac inflammatory genes and impairing PGC-1? mediated gene transcription of downstream transcription factors in type 2 diabetic hearts at an advanced age. PMID:23936397

Botta, Amy; Laher, Ismail; Beam, Julianne; DeCoffe, Daniella; Brown, Kirsty; Halder, Swagata; Devlin, Angela; Gibson, Deanna L.; Ghosh, Sanjoy

2013-01-01

70

Efficient mitochondrial biogenesis drives incomplete penetrance in Leber’s hereditary optic neuropathy  

PubMed Central

Leber’s hereditary optic neuropathy is a maternally inherited blinding disease caused as a result of homoplasmic point mutations in complex I subunit genes of mitochondrial DNA. It is characterized by incomplete penetrance, as only some mutation carriers become affected. Thus, the mitochondrial DNA mutation is necessary but not sufficient to cause optic neuropathy. Environmental triggers and genetic modifying factors have been considered to explain its variable penetrance. We measured the mitochondrial DNA copy number and mitochondrial mass indicators in blood cells from affected and carrier individuals, screening three large pedigrees and 39 independently collected smaller families with Leber’s hereditary optic neuropathy, as well as muscle biopsies and cells isolated by laser capturing from post-mortem specimens of retina and optic nerves, the latter being the disease targets. We show that unaffected mutation carriers have a significantly higher mitochondrial DNA copy number and mitochondrial mass compared with their affected relatives and control individuals. Comparative studies of fibroblasts from affected, carriers and controls, under different paradigms of metabolic demand, show that carriers display the highest capacity for activating mitochondrial biogenesis. Therefore we postulate that the increased mitochondrial biogenesis in carriers may overcome some of the pathogenic effect of mitochondrial DNA mutations. Screening of a few selected genetic variants in candidate genes involved in mitochondrial biogenesis failed to reveal any significant association. Our study provides a valuable mechanism to explain variability of penetrance in Leber’s hereditary optic neuropathy and clues for high throughput genetic screening to identify the nuclear modifying gene(s), opening an avenue to develop predictive genetic tests on disease risk and therapeutic strategies. PMID:24369379

Iommarini, Luisa; Giordano, Luca; Maresca, Alessandra; Pisano, Annalinda; Valentino, Maria Lucia; Caporali, Leonardo; Liguori, Rocco; Deceglie, Stefania; Roberti, Marina; Fanelli, Francesca; Fracasso, Flavio; Ross-Cisneros, Fred N.; D’Adamo, Pio; Hudson, Gavin; Pyle, Angela; Yu-Wai-Man, Patrick; Chinnery, Patrick F.; Zeviani, Massimo; Salomao, Solange R.; Berezovsky, Adriana; Belfort, Rubens; Ventura, Dora Fix; Moraes, Milton; Moraes Filho, Milton; Barboni, Piero; Sadun, Federico; De Negri, Annamaria; Sadun, Alfredo A.; Tancredi, Andrea; Mancini, Massimiliano; d’Amati, Giulia; Loguercio Polosa, Paola; Cantatore, Palmiro

2014-01-01

71

Efficient mitochondrial biogenesis drives incomplete penetrance in Leber's hereditary optic neuropathy.  

PubMed

Leber's hereditary optic neuropathy is a maternally inherited blinding disease caused as a result of homoplasmic point mutations in complex I subunit genes of mitochondrial DNA. It is characterized by incomplete penetrance, as only some mutation carriers become affected. Thus, the mitochondrial DNA mutation is necessary but not sufficient to cause optic neuropathy. Environmental triggers and genetic modifying factors have been considered to explain its variable penetrance. We measured the mitochondrial DNA copy number and mitochondrial mass indicators in blood cells from affected and carrier individuals, screening three large pedigrees and 39 independently collected smaller families with Leber's hereditary optic neuropathy, as well as muscle biopsies and cells isolated by laser capturing from post-mortem specimens of retina and optic nerves, the latter being the disease targets. We show that unaffected mutation carriers have a significantly higher mitochondrial DNA copy number and mitochondrial mass compared with their affected relatives and control individuals. Comparative studies of fibroblasts from affected, carriers and controls, under different paradigms of metabolic demand, show that carriers display the highest capacity for activating mitochondrial biogenesis. Therefore we postulate that the increased mitochondrial biogenesis in carriers may overcome some of the pathogenic effect of mitochondrial DNA mutations. Screening of a few selected genetic variants in candidate genes involved in mitochondrial biogenesis failed to reveal any significant association. Our study provides a valuable mechanism to explain variability of penetrance in Leber's hereditary optic neuropathy and clues for high throughput genetic screening to identify the nuclear modifying gene(s), opening an avenue to develop predictive genetic tests on disease risk and therapeutic strategies. PMID:24369379

Giordano, Carla; Iommarini, Luisa; Giordano, Luca; Maresca, Alessandra; Pisano, Annalinda; Valentino, Maria Lucia; Caporali, Leonardo; Liguori, Rocco; Deceglie, Stefania; Roberti, Marina; Fanelli, Francesca; Fracasso, Flavio; Ross-Cisneros, Fred N; D'Adamo, Pio; Hudson, Gavin; Pyle, Angela; Yu-Wai-Man, Patrick; Chinnery, Patrick F; Zeviani, Massimo; Salomao, Solange R; Berezovsky, Adriana; Belfort, Rubens; Ventura, Dora Fix; Moraes, Milton; Moraes Filho, Milton; Barboni, Piero; Sadun, Federico; De Negri, Annamaria; Sadun, Alfredo A; Tancredi, Andrea; Mancini, Massimiliano; d'Amati, Giulia; Loguercio Polosa, Paola; Cantatore, Palmiro; Carelli, Valerio

2014-02-01

72

Valproic acid triggers increased mitochondrial biogenesis in POLG-deficient fibroblasts  

PubMed Central

Valproic acid (VPA) is a widely used antiepileptic drug and also prescribed to treat migraine, chronic headache and bipolar disorder. Although it is usually well tolerated, a severe hepatotoxic reaction has been repeatedly reported after VPA administration. A profound toxic reaction on administration of VPA has been observed in several patients carrying POLG mutations, and heterozygous genetic variation in POLG has been strongly associated with VPA-induced liver toxicity. Here we studied the effect of VPA in fibroblasts of five patients carrying pathogenic mutations in the POLG gene. VPA administration caused a significant increase in the expression of POLG and several regulators of mitochondrial biogenesis. It was further supported by elevated mtDNA copy numbers. The effect of VPA on mitochondrial biogenesis was observed in both control and patient cell lines, but the capacity of mutant POLG to increase the expression of mitochondrial genes and to increase mtDNA copy numbers was less effective. No evidence of substantive differences in DNA methylation across the genome was observed between POLG mutated patients and controls. Given the marked perturbation of gene expression observed in the cell lines studied, we conclude that altered DNA methylation is unlikely to make a major contribution to POLG-mediated VPA toxicity. Our data provide experimental evidence that VPA triggers increased mitochondrial biogenesis by altering the expression of several mitochondrial genes; however, the capacity of POLG-deficient liver cells to address the increased metabolic rate caused by VPA administration is significantly impaired. PMID:24725338

Sitarz, Kamil S.; Elliott, Hannah R.; Karaman, Betül S.; Relton, Caroline; Chinnery, Patrick F.; Horvath, Rita

2014-01-01

73

Valproic acid triggers increased mitochondrial biogenesis in POLG-deficient fibroblasts.  

PubMed

Valproic acid (VPA) is a widely used antiepileptic drug and also prescribed to treat migraine, chronic headache and bipolar disorder. Although it is usually well tolerated, a severe hepatotoxic reaction has been repeatedly reported after VPA administration. A profound toxic reaction on administration of VPA has been observed in several patients carrying POLG mutations, and heterozygous genetic variation in POLG has been strongly associated with VPA-induced liver toxicity. Here we studied the effect of VPA in fibroblasts of five patients carrying pathogenic mutations in the POLG gene. VPA administration caused a significant increase in the expression of POLG and several regulators of mitochondrial biogenesis. It was further supported by elevated mtDNA copy numbers. The effect of VPA on mitochondrial biogenesis was observed in both control and patient cell lines, but the capacity of mutant POLG to increase the expression of mitochondrial genes and to increase mtDNA copy numbers was less effective. No evidence of substantive differences in DNA methylation across the genome was observed between POLG mutated patients and controls. Given the marked perturbation of gene expression observed in the cell lines studied, we conclude that altered DNA methylation is unlikely to make a major contribution to POLG-mediated VPA toxicity. Our data provide experimental evidence that VPA triggers increased mitochondrial biogenesis by altering the expression of several mitochondrial genes; however, the capacity of POLG-deficient liver cells to address the increased metabolic rate caused by VPA administration is significantly impaired. PMID:24725338

Sitarz, Kamil S; Elliott, Hannah R; Karaman, Betül S; Relton, Caroline; Chinnery, Patrick F; Horvath, Rita

2014-05-01

74

Leucine Modulates Mitochondrial Biogenesis and SIRT1-AMPK Signaling in C2C12 Myotubes  

PubMed Central

Previous studies from this laboratory demonstrate that dietary leucine protects against high fat diet-induced mitochondrial impairments and stimulates mitochondrial biogenesis and energy partitioning from adipocytes to muscle cells through SIRT1-mediated mechanisms. Moreover, ?-hydroxy-?-methyl butyrate (HMB), a metabolite of leucine, has been reported to activate AMPK synergistically with resveratrol in C2C12 myotubes. Therefore, we hypothesize that leucine-induced activation of SIRT1 and AMPK is the central event that links the upregulated mitochondrial biogenesis and fatty acid oxidation in skeletal muscle. Thus, C2C12 myotubes were treated with leucine (0.5?mM), alanine (0.5?mM), valine (0.5?mM), EX527 (SIRT1 inhibitor, 25??M), and Compound C (AMPK inhibitor, 25??M) alone or in combination to determine the roles of AMPK and SIRT1 in leucine-modulation of energy metabolism. Leucine significantly increased mitochondrial content, mitochondrial biogenesis-related genes expression, fatty acid oxidation, SIRT1 activity and gene expression, and AMPK phosphorylation in C2C12 myotubes compared to the controls, while EX527 and Compound C markedly attenuated these effects. Furthermore, leucine treatment for 24 hours resulted in time-dependent increases in cellular NAD+, SIRT1 activity, and p-AMPK level, with SIRT1 activation preceding that of AMPK, indicating that leucine activation of SIRT1, rather than AMPK, is the primary event. PMID:25400942

Liang, Chunzi; Curry, Benjamin J.; Brown, Patricia L.; Zemel, Michael B.

2014-01-01

75

Altered skeletal muscle mitochondrial biogenesis but improved endurance capacity in trained OPA1-deficient mice  

PubMed Central

The role of OPA1, a GTPase dynamin protein mainly involved in the fusion of inner mitochondrial membranes, has been studied in many cell types, but only a few studies have been conducted on adult differentiated tissues such as cardiac or skeletal muscle cells. Yet OPA1 is highly expressed in these cells, and could play different roles, especially in response to an environmental stress like exercise. Endurance exercise increases energy demand in skeletal muscle and repeated activity induces mitochondrial biogenesis and activation of fusion–fission cycles for the synthesis of new mitochondria. But currently no study has clearly shown a link between mitochondrial dynamics and biogenesis. Using a mouse model of haploinsufficiency for the Opa1 gene (Opa1+/?), we therefore studied the impact of OPA1 deficiency on the adaptation ability of fast skeletal muscles to endurance exercise training. Our results show that, surprisingly, Opa1+/? mice were able to perform the same physical activity as control mice. However, the adaptation strategies of both strains after training differed: while in control mice mitochondrial biogenesis was increased as expected, in Opa1+/? mice this process was blunted. Instead, training in Opa1+/? mice led to an increase in endurance capacity, and a specific adaptive response involving a metabolic remodelling towards enhanced fatty acid utilization. In conclusion, OPA1 appears necessary for the normal adaptive response and mitochondrial biogenesis of skeletal muscle to training. This work opens new perspectives on the role of mitochondrial dynamics in skeletal muscle cells and during adaptation to stress. PMID:24042504

Caffin, F; Prola, A; Piquereau, J; Novotova, M; David, DJ; Garnier, A; Fortin, D; Alavi, MV; Veksler, V; Ventura-Clapier, R; Joubert, F

2013-01-01

76

Mitochondrial Biogenesis: Regulation By Endogenous Gases during Inflammation and Organ Stress  

PubMed Central

The influence of mitochondrial dysfunction on pathological states involving inflammatory and/or oxidative stress in tissues that do not show frank cellular apoptosis or necrosis has been rather difficult to unravel, and the literature is replete with contradictory information. Although such discrepancies have many potential causes related to the type of injurious agent, the severity and duration of the injury, and the particular cells and tissues and the functions involved, it is the successful induction of cellular adaptive responses that ultimately governs the resolution of mitochondrial dysfunction and survival of the cell. Much recent attention has been devoted to unraveling the signaling pathways that activate mitochondrial biogenesis and other processes involved in mitochondrial quality control (QC) during inflammatory and oxidative stress with an eye towards the development of novel targets for therapeutic mitigation of the resultant tissue damage. This review provides a brief overview of this emerging field with an emphasis on the role of signaling through the endogenous gases (NO, CO and H2S) and a redox-based approach that brings transparency to key factors that contribute to the resolution of mitochondrial dysfunction and the maintenance of cell vitality. We make the case that targeted stimulation of mitochondrial biogenesis could be a potentially valuable approach for the development of new therapies for the treatment of diseases for which mitochondrial damage is a major consideration. PMID:24606800

Suliman, Hagir B.; Piantadosi, Claude A.

2014-01-01

77

Molecular chaperones as essential mediators of mitochondrial biogenesis  

Microsoft Academic Search

Chaperone proteins have been initially identified by their ability to confer cellular resistance to various stress conditions. However, molecular chaperones participate also in many constitutive cellular processes. Mitochondria contain several members of the major chaperone families that have important functions in maintaining mitochondrial function. The major Hsp70 of the mitochondrial matrix (mtHsp70) is essential for the translocation of cytosolic precursor

Wolfgang Voos; Karin Röttgers

2002-01-01

78

GCN5-like protein 1 (GCN5L1) controls mitochondrial content through coordinated regulation of mitochondrial biogenesis and mitophagy.  

PubMed

Cellular mitochondrial content is governed by the competing processes of organelle biogenesis and degradation. It is proposed that these programs are tightly regulated to ensure that the cell maintains sufficient organelles to meet its biosynthetic, energetic, and other homeostatic requirements. We recently reported that GCN5L1, a putative nutrient-sensing regulator, controls mitochondrial removal by autophagy. Here we show that genetic deletion of GCN5L1 has a direct positive effect on the expression and activity of Transcriptional Factor EB (TFEB), which acts as a master regulator of autophagy. Surprisingly, the induction of TFEB-mediated autophagy pathways does not diminish cellular mitochondrial content, as its activity is countered by induction of the mitochondrial biogenesis transcriptional co-activator PPAR? coactivator 1? (PGC-1?). Concurrent induction of the TFEB and PGC-1? pathways results in an increased mitochondrial turnover rate in GCN5L1(-/-) cells. Finally, we show that genetic knockdown of either TFEB or PGC-1? leads to a corresponding decrease in the expression of the other gene, indicating that these proteins act coordinately, and in opposition, to maintain cellular mitochondrial content in response to the modulation of nutrient-sensing signatures. PMID:24356961

Scott, Iain; Webster, Bradley R; Chan, Carmen K; Okonkwo, Joshua U; Han, Kim; Sack, Michael N

2014-01-31

79

GCN5-like Protein 1 (GCN5L1) Controls Mitochondrial Content through Coordinated Regulation of Mitochondrial Biogenesis and Mitophagy*  

PubMed Central

Cellular mitochondrial content is governed by the competing processes of organelle biogenesis and degradation. It is proposed that these programs are tightly regulated to ensure that the cell maintains sufficient organelles to meet its biosynthetic, energetic, and other homeostatic requirements. We recently reported that GCN5L1, a putative nutrient-sensing regulator, controls mitochondrial removal by autophagy. Here we show that genetic deletion of GCN5L1 has a direct positive effect on the expression and activity of Transcriptional Factor EB (TFEB), which acts as a master regulator of autophagy. Surprisingly, the induction of TFEB-mediated autophagy pathways does not diminish cellular mitochondrial content, as its activity is countered by induction of the mitochondrial biogenesis transcriptional co-activator PPAR? coactivator 1? (PGC-1?). Concurrent induction of the TFEB and PGC-1? pathways results in an increased mitochondrial turnover rate in GCN5L1?/? cells. Finally, we show that genetic knockdown of either TFEB or PGC-1? leads to a corresponding decrease in the expression of the other gene, indicating that these proteins act coordinately, and in opposition, to maintain cellular mitochondrial content in response to the modulation of nutrient-sensing signatures. PMID:24356961

Scott, Iain; Webster, Bradley R.; Chan, Carmen K.; Okonkwo, Joshua U.; Han, Kim; Sack, Michael N.

2014-01-01

80

Optimizing Intramuscular Adaptations to Aerobic Exercise: Effects of Carbohydrate Restriction and Protein Supplementation on Mitochondrial Biogenesis12  

PubMed Central

Mitochondrial biogenesis is a critical metabolic adaptation to aerobic exercise training that results in enhanced mitochondrial size, content, number, and activity. Recent evidence has shown that dietary manipulation can further enhance mitochondrial adaptations to aerobic exercise training, which may delay skeletal muscle fatigue and enhance exercise performance. Specifically, studies have demonstrated that combining carbohydrate restriction (endogenous and exogenous) with a single bout of aerobic exercise potentiates the beneficial effects of exercise on markers of mitochondrial biogenesis. Additionally, studies have demonstrated that high-quality protein supplementation enhances anabolic skeletal muscle intracellular signaling and mitochondrial protein synthesis following a single bout of aerobic exercise. Mitochondrial biogenesis is stimulated by complex intracellular signaling pathways that appear to be primarily regulated by 5?AMP-activated protein kinase and p38 mitogen-activated protein kinase mediated through proliferator-activated ? receptor co-activator 1 ? activation, resulting in increased mitochondrial DNA expression and enhanced skeletal muscle oxidative capacity. However, the mechanisms by which concomitant carbohydrate restriction and dietary protein supplementation modulates mitochondrial adaptations to aerobic exercise training remains unclear. This review summarizes intracellular regulation of mitochondrial biogenesis and the effects of carbohydrate restriction and protein supplementation on mitochondrial adaptations to aerobic exercise. PMID:24228194

Margolis, Lee M.; Pasiakos, Stefan M.

2013-01-01

81

Tetramethylpyrazine Ameliorates High Glucose-Induced Endothelial Dysfunction by Increasing Mitochondrial Biogenesis  

PubMed Central

Tetramethylpyrazine (TMP) is an active compound isolated from a Chinese herbal prescription that is widely used in traditional Chinese medicine for the treatment of inflammatory and cardiovascular diseases. We have previously reported that TMP acts as a potent antioxidant protecting endothelial cells against high glucose-induced damages. However, the molecular mechanism responsible for the antioxidant effect of TMP remains to be elucidated. In this study, we show that TMP increases nitric oxide production in endothelial cells and promotes endothelium-dependent relaxation in rate aortic rings. The antioxidant effect of TMP appears attributable to its ability to activate the mitochondrial biogenesis, as reflected in an up-regulation of complex III and amelioration of mitochondrial membrane potential. Furthermore, TMP is able to reverse high glucose-induced suppression of SIRT1 and the biogenesis-related factors, including PGC-1?, NRF1 and TFAM, suggesting a new molecular mechanism underlying the protective effect of TMP on the endothelium. PMID:24505445

Xu, Qiong; Xia, Pu; Li, Xi; Wang, Wei; Liu, Zhenqi; Gao, Xin

2014-01-01

82

The mitochondrial import protein Mim1 promotes biogenesis of multispanning outer membrane proteins  

PubMed Central

The mitochondrial outer membrane contains translocase complexes for the import of precursor proteins. The translocase of the outer membrane complex functions as a general preprotein entry gate, whereas the sorting and assembly machinery complex mediates membrane insertion of ?-barrel proteins of the outer membrane. Several ?-helical outer membrane proteins are known to carry multiple transmembrane segments; however, only limited information is available on the biogenesis of these proteins. We report that mitochondria lacking the mitochondrial import protein 1 (Mim1) are impaired in the biogenesis of multispanning outer membrane proteins, whereas overexpression of Mim1 stimulates their import. The Mim1 complex cooperates with the receptor Tom70 in binding of precursor proteins and promotes their insertion and assembly into the outer membrane. We conclude that the Mim1 complex plays a central role in the import of ?-helical outer membrane proteins with multiple transmembrane segments. PMID:21825073

Becker, Thomas; Wenz, Lena-Sophie; Krüger, Vivien; Lehmann, Waltraut; Müller, Judith M.; Goroncy, Luise; Zufall, Nicole; Lithgow, Trevor; Guiard, Bernard; Chacinska, Agnieszka; Wagner, Richard; Meisinger, Chris

2011-01-01

83

Complementary action of the PGC1 coactivators in mitochondrial biogenesis and brown fat differentiation  

Microsoft Academic Search

Summary Mitochondria play an essential role in the ability of brown fat to generate heat, and the PGC-1 coactivators control several aspects of mitochondrial biogenesis. To investigate their specific roles in brown fat cells, we generated immortal preadipo- cyte lines from the brown adipose tissue of mice lacking PGC-1a. We could then efficiently knockdown PGC-1b expression by shRNA expression. Loss

Marc Uldry; Wenli Yang; Julie St-Pierre; Jiandie Lin; Patrick Seale; Bruce M. Spiegelman

2006-01-01

84

Perfluorooctanoate, perflourooctanesulfonate, and N-ethyl perfluorooctanesulfonamido ethanol; peroxisome proliferation and mitochondrial biogenesis  

Microsoft Academic Search

Compounds that cause peroxisome proliferation in rats and mice have been reported to interfere with mitochondrial (mt) bioenergetics and possibly biogenesis. The purpose of this investigation was to establish whether proliferation of peroxisomes and mitochondria are necessarily related. Perfluorooctanesulfonate (PFOS) and N-ethyl perfluorooctanesulfonamido ethanol (N-EtFOSE) were investigated as peroxisome proliferators in comparison to perfluorooctanoic acid (PFOA). Three parameters were chosen

Jessica Berthiaume; Kendall B Wallace

2002-01-01

85

Coordination of PGC1? and iron uptake in mitochondrial biogenesis and osteoclast activation  

Microsoft Academic Search

Osteoclasts are acid-secreting polykaryons that have high energy demands and contain abundant mitochondria. How mitochondrial biogenesis is integrated with osteoclast differentiation is unknown. We found that the transcription of Ppargc1b, which encodes peroxisome proliferator–activated receptor-? coactivator 1? (PGC-1?), was induced during osteoclast differentiation by cAMP response element–binding protein (CREB) as a result of reactive oxygen species. Knockdown of Ppargc1b in

Kiyo-aki Ishii; Toshio Fumoto; Kazuhiro Iwai; Sunao Takeshita; Masako Ito; Nobuyuki Shimohata; Hiroyuki Aburatani; Shigeru Taketani; Christopher J Lelliott; Antonio Vidal-Puig; Kyoji Ikeda

2009-01-01

86

Calorie Restriction Promotes Mitochondrial Biogenesis by Inducing the Expression of eNOS  

Microsoft Academic Search

Calorie restriction extends life span in organisms ranging from yeast to mammals. Here, we report that calorie restriction for either 3 or 12 months induced endothelial nitric oxide synthase (eNOS) expression and 3',5'-cyclic guanosine monophosphate formation in various tissues of male mice. This was accompanied by mitochondrial biogenesis, with increased oxygen consumption and adenosine triphosphate production, and an enhanced expression

Enzo Nisoli; Cristina Tonello; Annalisa Cardile; Valeria Cozzi; Renata Bracale; Laura Tedesco; Sestina Falcone; Alessandra Valerio; Orazio Cantoni; Emilio Clementi; Salvador Moncada; Michele O. Carruba

2005-01-01

87

Berberine protects against high fat diet-induced dysfunction in muscle mitochondria by inducing SIRT1-dependent mitochondrial biogenesis  

PubMed Central

Berberine (BBR) has recently been shown to improve insulin sensitivity in rodent models of insulin resistance. Although this effect was explained partly through an observed activation of AMP-activated protein kinase (AMPK), the upstream and downstream mediators of this phenotype were not explored. Here, we show that BBR supplementation reverts mitochondrial dysfunction induced by High Fat Diet (HFD) and hyperglycemia in skeletal muscle, in part due to an increase in mitochondrial biogenesis. Furthermore, we observe that the prevention of mitochondrial dysfunction by BBR, the increase in mitochondrial biogenesis, as well as BBR-induced AMPK activation, are blocked in cells in which SIRT1 has been knocked-down. Taken together, these data reveal an important role for SIRT1 and mitochondrial biogenesis in the preventive effects of BBR on diet-induced insulin resistance. PMID:22027215

Gomes, Ana P.; Duarte, Filipe V.; Nunes, Patricia; Hubbard, Basil P.; Teodoro, João S.; Varela, Ana T.; Jones, John G.; Sinclair, David A.; Palmeira, Carlos M.; Rolo, Anabela P.

2012-01-01

88

Exercise, but not quercetin, ameliorates inflammation, mitochondrial biogenesis, and lipid metabolism in skeletal muscle after strenuous exercise by high-fat diet mice  

PubMed Central

[Purpose] The purpose of this study was to investigate whether moderate exercise and quercetin intake with a low fat diet contribute to inflammatory cytokine production, mitochondrial biogenesis, and lipid metabolism in skeletal muscle after strenuous exercise by high-fat diet mice. [Methods] Male C57BL/6 mice were randomly divided into four groups: (1) High-fat for 12 weeks and low-fat diet control (C; n = 6); (2) high-fat diet for 12 weeks and low-fat diet with quercetin (Q; n = 4); (3) high-fat diet for 12 weeks and low-fat diet with exercise (E; n = 4); or (4) high-fat diet for 12 weeks and low-fat diet with exercise and quercetin (EQ; n = 5). Quercetin (10 mg/kg) was administered once per day, 5 day/week for 8 weeks. Exercise training was performed at moderate intensity for 8 weeks, 5 days/week for 30–60 min/day. Mice were subjected to a strenuous exercise bout of 60 min at a speed of 25 m/min (VO2 max 85%) conducted as an exercise-induced fatigue just before sacrifice. [Results] As results, body weights were significantly different among the groups. Exercise training significantly reduced inflammatory cytokines after strenuous exercise in skeletal muscle of high-fat diet mice. Exercise training increased Tfam mRNA in the soleus muscle after strenuous exercise. Exercise training significantly decreased lipogenesis markers in skeletal muscle of obese mice after strenuous exercise. Moderate exercise significantly increased lipolysis markers in the tibialis anterior muscle. [Conclusion] These findings suggest that exercise training reduced inflammatory cytokine levels and improved mitochondrial biogenesis and lipid metabolism. However quercetin supplementation did not affect these parameters. Thus, long-term moderate exercise training has positive effects on obesity.

Kwon, Soon Mi; Park, Hee Geun; Jun, Jong Kui; Lee, Wang Lok

2014-01-01

89

Myc controls transcriptional regulation of cardiac metabolism and mitochondrial biogenesis in response to pathological stress in mice  

PubMed Central

In the adult heart, regulation of fatty acid oxidation and mitochondrial genes is controlled by the PPAR? coactivator–1 (PGC-1) family of transcriptional coactivators. However, in response to pathological stressors such as hemodynamic load or ischemia, cardiac myocytes downregulate PGC-1 activity and fatty acid oxidation genes in preference for glucose metabolism pathways. Interestingly, despite the reduced PGC-1 activity, these pathological stressors are associated with mitochondrial biogenesis, at least initially. The transcription factors that regulate these changes in the setting of reduced PGC-1 are unknown, but Myc can regulate glucose metabolism and mitochondrial biogenesis during cell proliferation and tumorigenesis in cancer cells. Here we have demonstrated that Myc activation in the myocardium of adult mice increases glucose uptake and utilization, downregulates fatty acid oxidation by reducing PGC-1? levels, and induces mitochondrial biogenesis. Inactivation of Myc in the adult myocardium attenuated hypertrophic growth and decreased the expression of glycolytic and mitochondrial biogenesis genes in response to hemodynamic load. Surprisingly, the Myc-orchestrated metabolic alterations were associated with preserved cardiac function and improved recovery from ischemia. Our data suggest that Myc directly regulates glucose metabolism and mitochondrial biogenesis in cardiac myocytes and is an important regulator of energy metabolism in the heart in response to pathologic stress. PMID:20364083

Ahuja, Preeti; Zhao, Peng; Angelis, Ekaterini; Ruan, Hongmei; Korge, Paavo; Olson, Aaron; Wang, Yibin; Jin, Eunsook S.; Jeffrey, F. Mark; Portman, Michael; MacLellan, W. Robb

2010-01-01

90

Calorie Restriction Increases Muscle Mitochondrial Biogenesis in Healthy Humans  

Microsoft Academic Search

BackgroundCaloric restriction without malnutrition extends life span in a range of organisms including insects and mammals and lowers free radical production by the mitochondria. However, the mechanism responsible for this adaptation are poorly understood.Methods and FindingsThe current study was undertaken to examine muscle mitochondrial bioenergetics in response to caloric restriction alone or in combination with exercise in 36 young (36.8

Anthony E Civitarese; Stacy Carling; Leonie K Heilbronn; Mathew H Hulver; Barbara Ukropcova; Walter A Deutsch; Steven R Smith; Eric Ravussin

2007-01-01

91

Increased mitochondrial biogenesis in primary leukemia cells: the role of endogenous nitric oxide and impact on sensitivity to fludarabine  

Microsoft Academic Search

B cell chronic lymphocytic leukemia (CLL) is the most prevalent adult leukemia in the Western hemisphere, yet many biological and molecular features of the disease remain undefined. CLL cells generate increased levels of radical species such as superoxide and nitric oxide (NO), which is associated with mitochondrial DNA mutations. Considering that NO levels can affect mitochondrial biogenesis, we hypothesized that

J S Carew; S T Nawrocki; R H Xu; K Dunner; D J McConkey; W G Wierda; M J Keating; P Huang

2004-01-01

92

Developmental regulation of mitochondrial biogenesis and function in the mouse mammary gland during a prolonged lactation cycle  

Technology Transfer Automated Retrieval System (TEKTRAN)

The regulation of mitochondrial biogenesis and function in the lactating mammary cell is poorly understood. The goal of this study was to use proteomics to relate temporal changes in mammary cell mitochondrial function during lactation to changes in the proteins that make up this organelle. The hypo...

93

Suppression of oxidative metabolism and mitochondrial biogenesis by the transcriptional corepressor RIP140 in mouse adipocytes  

PubMed Central

Using an siRNA-based screen, we identified the transcriptional corepressor RIP140 as a negative regulator of insulin-responsive hexose uptake and oxidative metabolism in 3T3-L1 adipocytes. Affymetrix GeneChip profiling revealed that RIP140 depletion upregulates the expression of clusters of genes in the pathways of glucose uptake, glycolysis, TCA cycle, fatty acid oxidation, mitochondrial biogenesis, and oxidative phosphorylation in these cells. Conversely, we show that reexpression of RIP140 in mouse embryonic fibroblasts derived from RIP140-null mice downregulates expression of many of these same genes. Consistent with these microarray data, RIP140 gene silencing in cultured adipocytes increased both conversion of [14C]glucose to CO2 and mitochondrial oxygen consumption. RIP140-null mice, previously reported to resist weight gain on a high-fat diet, are shown here to display enhanced glucose tolerance and enhanced responsiveness to insulin compared with matched wild-type mice upon high-fat feeding. Mechanistically, RIP140 was found to require the nuclear receptor ERR? to regulate hexose uptake and mitochondrial proteins SDHB and CoxVb, although it likely acts through other nuclear receptors as well. We conclude that RIP140 is a major suppressor of adipocyte oxidative metabolism and mitochondrial biogenesis, as well as a negative regulator of whole-body glucose tolerance and energy expenditure in mice. PMID:16374519

Powelka, Aimee M.; Seth, Asha; Virbasius, Joseph V.; Kiskinis, Evangelos; Nicoloro, Sarah M.; Guilherme, Adilson; Tang, Xiaoqing; Straubhaar, Juerg; Cherniack, Andrew D.; Parker, Malcolm G.; Czech, Michael P.

2005-01-01

94

The role of AMPK in controlling metabolism and mitochondrial biogenesis during exercise.  

PubMed

Insulin resistance is associated with defects in skeletal muscle fatty acid (FA) metabolism that contribute to the development of type 2 diabetes. Endurance exercise increases FA and glucose metabolism, muscle mitochondrial content and insulin sensitivity. In skeletal muscle, basal rates of FA oxidation are dependent on AMP-activated protein kinase (AMPK) phosphorylation of acetyl-CoA carboxylase 2, the rate-limiting enzyme controlling the production of the metabolic intermediate malonyl-CoA. Likewise, AMPK is essential for maintaining muscle mitochondrial content in untrained mice; effects that may be mediated through regulation of the peroxisome proliferator-activated receptor ? co-activator-1?. However, the importance of AMPK in regulating glucose and FA uptake, FA oxidation and mitochondrial biogenesis during and following endurance exercise training is not fully understood. A better understanding of the mechanisms by which endurance exercise regulates substrate utilization and mitochondrial biogenesis may lead to improved therapeutic and preventative strategies for the treatment of insulin resistance and type 2 diabetes. PMID:25261498

Marcinko, Katarina; Steinberg, Gregory R

2014-12-01

95

Eriocitrin ameliorates diet-induced hepatic steatosis with activation of mitochondrial biogenesis  

PubMed Central

Lemon (Citrus limon) contains various bioactive flavonoids, and prevents obesity and obesity-associated metabolic diseases. We focused on eriocitrin (eriodictyol 7-rutinoside), a powerful antioxidative flavonoid in lemon with lipid-lowering effects in a rat model of high-fat diet. To investigate the mechanism of action of eriocitrin, we conducted feeding experiments on zebrafish with diet-induced obesity. Oral administration of eriocitrin (32?mg/kg/day for 28 days) improved dyslipidaemia and decreased lipid droplets in the liver. DNA microarray analysis revealed that eriocitrin increased mRNA of mitochondrial biogenesis genes, such as mitochondria transcription factor, nuclear respiratory factor 1, cytochrome c oxidase subunit 4, and ATP synthase. In HepG2 cells, eriocitrin also induced the corresponding orthologues, and reduced lipid accumulation under conditions of lipid loading. Eriocitrin increased mitochondrial size and mtDNA content, which resulted in ATP production in HepG2 cells and zebrafish. In summary, dietary eriocitrin ameliorates diet-induced hepatic steatosis with activation of mitochondrial biogenesis. PMID:24424211

Hiramitsu, Masanori; Shimada, Yasuhito; Kuroyanagi, Junya; Inoue, Takashi; Katagiri, Takao; Zang, Liqing; Nishimura, Yuhei; Nishimura, Norihiro; Tanaka, Toshio

2014-01-01

96

cGMP-selective phosphodiesterase inhibitors stimulate mitochondrial biogenesis and promote recovery from acute kidney injury.  

PubMed

Recent studies demonstrate that mitochondrial dysfunction is a mediator of acute kidney injury (AKI). Consequently, restoration of mitochondrial function after AKI may be key to the recovery of renal function. Mitochondrial function can be restored through the generation of new, functional mitochondria in a process called mitochondrial biogenesis (MB). Despite its potential therapeutic significance, very few pharmacological agents have been identified to induce MB. To examine the efficacy of phosphodiesterase (PDE) inhibitors (PDE3: cAMP and cGMP activity; and PDE4: cAMP activity) in stimulating MB, primary cultures of renal proximal tubular cells (RPTCs) were treated with a panel of inhibitors for 24 hours. PDE3, but not PDE4, inhibitors increased the FCCP-uncoupled oxygen consumption rate (OCR), a marker of MB. Exposure of RPTCs to the PDE3 inhibitors, cilostamide and trequinsin, for 24 hours increased peroxisome proliferator-activated receptor ? coactivator-1?, and multiple mitochondrial electron transport chain genes. Cilostamide and trequinsin also increased mRNA expression of mitochondrial genes and mitochondrial DNA copy number in mice renal cortex. Consistent with these experiments, 8-Br-cGMP increased FCCP-uncoupled OCR and mitochondrial gene expression, whereas 8-Br-cAMP had no effect. The cGMP-specific PDE5 inhibitor sildenafil also induced MB in RPTCs and in vivo in mouse renal cortex. Treatment of mice with sildenafil after folic acid-induced AKI promoted restoration of MB and renal recovery. These data provide strong evidence that specific PDE inhibitors that increase cGMP are inducers of MB in vitro and in vivo, and suggest their potential efficacy in AKI and other diseases characterized by mitochondrial dysfunction and suppressed MB. PMID:24042162

Whitaker, Ryan M; Wills, Lauren P; Stallons, L Jay; Schnellmann, Rick G

2013-12-01

97

PhD position: Mitochondrial Biogenesis in Parasitic Protozoa Applications are invited for a Ph. D. Student position, funded by the Swiss National  

E-print Network

PhD position: Mitochondrial Biogenesis in Parasitic Protozoa Applications are invited for a Ph. D at the University of Bern/Switzerland. We are a highly motivated research group that studies mitochondrial biogenesis using the parasitic protozoa Trypanosoma brucei as model. Unlike most other eukaryotes

Mühlemann, Oliver

98

Hypothalamic-pituitary-thyroid axis hormones stimulate mitochondrial function and biogenesis in human hair follicles.  

PubMed

Thyroid hormones regulate mitochondrial function. As other hypothalamic-pituitary-thyroid (HPT) axis hormones, i.e., thyrotropin-releasing hormone (TRH) and thyrotropin (TSH), are expressed in human hair follicles (HFs) and regulate mitochondrial function in human epidermis, we investigated in organ-cultured human scalp HFs whether TRH (30 nM), TSH (10 mU ml(-1)), thyroxine (T4) (100 nM), and triiodothyronine (T3) (100 pM) alter intrafollicular mitochondrial energy metabolism. All HPT-axis members increased gene and protein expression of mitochondrial-encoded subunit 1 of cytochrome c oxidase (MTCO1), a subunit of respiratory chain complex IV, mitochondrial transcription factor A (TFAM), and Porin. All hormones also stimulated intrafollicular complex I/IV activity and mitochondrial biogenesis. The TSH effects on MTCO1, TFAM, and porin could be abolished by K1-70, a TSH-receptor antagonist, suggesting a TSH receptor-mediated action. Notably, as measured by calorimetry, T3 and TSH increased follicular heat production, whereas T3/T4 and TRH stimulated ATP production in cultured HF keratinocytes. HPT-axis hormones did not increase reactive oxygen species (ROS) production. Rather, T3 and T4 reduced ROS formation, and all tested HPT-axis hormones increased the transcription of ROS scavengers (catalase, superoxide dismutase 2) in HF keratinocytes. Thus, mitochondrial biology, energy metabolism, and redox state of human HFs are subject to profound (neuro-)endocrine regulation by HPT-axis hormones. The neuroendocrine control of mitochondrial biology in a complex human mini-organ revealed here may be therapeutically exploitable. PMID:23949722

Vidali, Silvia; Knuever, Jana; Lerchner, Johannes; Giesen, Melanie; Bíró, Tamás; Klinger, Matthias; Kofler, Barbara; Funk, Wolfgang; Poeggeler, Burkhard; Paus, Ralf

2014-01-01

99

Acetate supplementation increases brain phosphocreatine and reduces AMP levels with no effect on mitochondrial biogenesis  

PubMed Central

Acetate supplementation in rats increases plasma acetate and brain acetyl-CoA levels. Although acetate is used as a marker to study glial energy metabolism, the effect that acetate supplementation has on normal brain energy stores has not been quantified. To determine the effect(s) that an increase in acetyl-CoA levels has on brain energy metabolism, we measured brain nucleotide, phosphagen and glycogen levels, and quantified cardiolipin content and mitochondrial number in rats subjected to acetate supplementation. Acetate supplementation was induced with glyceryl triacetate (GTA) by oral gavage (6 g/Kg body weight). Rats used for biochemical analysis were euthanized using head-focused microwave irradiation at 2, and 4 hr following treatment to immediately stop metabolism. We found that acetate did not alter brain ATP, ADP, NAD, GTP levels, or the energy charge ratio [ECR, (ATP + ½ ADP) / (ATP + ADP + AMP)] when compared to controls. However, after 4 hr of treatment brain phosphocreatine levels were significantly elevated with a concomitant reduction in AMP levels with no change in glycogen levels. In parallel studies where rats were treated with GTA for 28 days, we found that acetate did not alter brain glycogen and mitochondrial biogenesis as determined by measuring brain cardiolipin content, the fatty acid composition of cardiolipin and using quantitative ultra-structural analysis to determine mitochondrial density/unit area of cytoplasm in hippocampal CA3 neurons. Collectively, these data suggest that an increase in brain acetyl-CoA levels by acetate supplementation does increase brain energy stores however it has no effect on brain glycogen and neuronal mitochondrial biogenesis. PMID:23321384

Bhatt, Dhaval P.; Houdek, Heidi M.; Watt, John A.; Rosenberger, Thad A.

2013-01-01

100

Metastasis suppressor KISS1 appears to reverse the Warburg effect by enhancing mitochondrial biogenesis  

PubMed Central

Cancer cells tend to utilize aerobic glycolysis even under normoxic conditions, commonly called the “Warburg Effect.” Aerobic glycolysis often directly correlates with malignancy, but its purpose, if any, in metastasis remains unclear. When wild-type KISS1 metastasis suppressor is expressed, aerobic glycolysis decreases and oxidative phosphorylation predominates. However, when KISS1 is missing the secretion signal peptide (?SS), invasion and metastasis are no longer suppressed and cells continue to metabolize using aerobic glycolysis. KISS1-expressing cells have 30–50% more mitochondrial mass than ?SS-expressing cells, which is accompanied by correspondingly increased mitochondrial gene expression and higher expression of PGC1?, a master co-activator that regulates mitochondrial mass and metabolism. PGC1?-mediated downstream pathways (i.e. fatty acid synthesis and ?-oxidation) are differentially regulated by KISS1, apparently reliant upon direct KISS1 interaction with NRF1, a major transcription factor involved in mitochondrial biogenesis. Since the downstream effects could be reversed using shRNA to KISS1 or PGC1?, these data appear to directly connect changes in mitochondria mass, cellular glucose metabolism and metastasis. PMID:24351292

Liu, Wen; Beck, Benjamin H.; Vaidya, Kedar S.; Nash, Kevin T.; Feeley, Kyle P.; Ballinger, Scott W.; Pounds, Keke M.; Denning, Warren L.; Diers, Anne R.; Landar, Aimee; Dhar, Animesh; Iwakuma, Tomoo; Welch, Danny R.

2014-01-01

101

Transcription-independent role for human mitochondrial RNA polymerase in mitochondrial ribosome biogenesis  

PubMed Central

Human mitochondrial RNA polymerase, POLRMT, is required for mitochondrial DNA (mtDNA) transcription and forms initiation complexes with human mitochondrial transcription factor B2 (h-mtTFB2). However, POLRMT also interacts with the paralogue of h-mtTFB2, h-mtTFB1, which is a 12S ribosomal RNA methyltransferase required for small (28S) mitochondrial ribosome subunit assembly. Herein, we show that POLRMT associates with h-mtTFB1 in 28S mitochondrial ribosome complexes that are stable in the absence of mitochondrial transcription and distinct from transcription complexes containing POLRMT and h-mtTFB2. Overexpression of POLRMT in HeLa cells increases 12S rRNA methylation by h-mtTFB1 and reduces the steady-state levels of mtDNA-encoded proteins and respiration, apparently because of a decrease in fully assembled 55S mitochondrial ribosomes. We propose that POLRMT interacts directly with h-mtTFB1 in 28S mitochondrial ribosomes to augment its 12S rRNA methyltransferase activity, and that together they provide a checkpoint for proper 28S and 55S mitochondrial ribosome assembly. Thus, POLRMT is multi-functional, forming distinct protein complexes that regulate different steps in mitochondrial gene expression, at least one of which does not involve transcription per se. The significance of these results is discussed with regard to the mechanism and regulation of human mitochondrial gene expression and the potential multi-functionality of RNA polymerases in general. PMID:23303773

Surovtseva, Yulia V.; Shadel, Gerald S.

2013-01-01

102

TSC-mTOR maintains quiescence and function of hematopoietic stem cells by repressing mitochondrial biogenesis and reactive oxygen species  

Microsoft Academic Search

The tuberous sclerosis complex (TSC) - mammalian target of rapamycin (mTOR) pathway is a key regulator of cellular metabolism. We used conditional deletion of Tsc1 to address how quiescence is associated with the function of hematopoietic stem cells (HSCs). We demonstrate that Tsc1 deletion in the HSCs drives them from quiescence into rapid cy- cling, with increased mitochondrial biogenesis and

Chong Chen; Yu Liu; Runhua Liu; Tsuneo Ikenoue; Kun-Liang Guan; Yang Liu; Pan Zheng

2008-01-01

103

Nuclear Recruitment of Neuronal Nitric-oxide Synthase by ?-Syntrophin Is Crucial for the Induction of Mitochondrial Biogenesis*  

PubMed Central

Neuronal nitric-oxide synthase (nNOS) has various splicing variants and different subcellular localizations. nNOS can be found also in the nucleus; however, its exact role in this compartment is still not completely defined. In this report, we demonstrate that the PDZ domain allows the recruitment of nNOS to nuclei, thus favoring local NO production, nuclear protein S-nitrosylation, and induction of mitochondrial biogenesis. In particular, overexpression of PDZ-containing nNOS (nNOS?) increases S-nitrosylated CREB with consequent augmented binding on cAMP response element consensus sequence on peroxisome proliferator-activated receptor ? co-activator (PGC)-1? promoter. The resulting PGC-1? induction is accompanied by the expression of mitochondrial genes (e.g., TFAM, MtCO1) and increased mitochondrial mass. Importantly, full active nNOS lacking PDZ domain (nNOS?) does not localize in nuclei and fails in inducing the expression of PGC-1?. Moreover, we substantiate that the mitochondrial biogenesis normally accompanying myogenesis is associated with nuclear translocation of nNOS. We demonstrate that ?-Syntrophin, which resides in nuclei of myocytes, functions as the upstream mediator of nuclear nNOS translocation and nNOS-dependent mitochondrial biogenesis. Overall, our results indicate that altered nNOS splicing and nuclear localization could be contributing factors in human muscular diseases associated with mitochondrial impairment. PMID:24235139

Aquilano, Katia; Baldelli, Sara; Ciriolo, Maria R.

2014-01-01

104

Resveratrol preserves mitochondrial function, stimulates mitochondrial biogenesis, and attenuates oxidative stress in regulatory T cells of mice fed a high-fat diet.  

PubMed

Consumption of high-fat diet (HFD) is related with increased oxidative stress and dysfunctional mitochondria in many organs. The effects of resveratrol (trans-3,5,4'-trihydroxystilbene) that can protect T lymphocytes in various disease conditions on the HFD-induced apoptosis of CD4(+) CD25(+) CD127(low/-) regulatory T cells (Tregs) were studied, and the possible mechanism was postulated. Resveratrol significantly decreased Tregs death induced by 20-wk HFD, being associated with the reduction of reactive oxygen species production and the alleviation of HFD-induced loss of mitochondrial membrane potential (??m) in Tregs. Furthermore, resveratrol increased the expression of factors that regulated mitochondrial biogenesis in Tregs. Finally, resveratrol recovered the HFD-induced activation of apoptotic markers in Tregs. Resveratrol protected Tregs against HFD-induced apoptosis by reducing oxidative stress, restoring mitochondrial functional activities, and stimulating mitochondrial biogenesis. PMID:25156660

Wang, Bin; Sun, Jin; Ma, Yuhua; Wu, Guirong; Tian, Yingjie; Shi, Yonghui; Le, Guowei

2014-09-01

105

Induction of mitochondrial biogenesis protects against caspase-dependent and caspase-independent apoptosis in L6 myoblasts.  

PubMed

Apoptotic signaling plays an important role in skeletal muscle degradation, atrophy, and dysfunction. Mitochondria are central executers of apoptosis by directly participating in caspase-dependent and caspase-independent cell death signaling. Given the important apoptotic role of mitochondria, altering mitochondrial content could influence apoptosis. Therefore, we examined the direct effect of modest, but physiological increases in mitochondrial biogenesis and content on skeletal muscle apoptosis using a cell culture approach. Treatment of L6 myoblasts with SNAP or AICAR (5h/day for 5days) significantly increased PGC-1, AIF, cytochrome c, and MnSOD protein content as well as MitoTracker staining. Following induction of mitochondrial biogenesis, L6 myoblasts displayed decreased sensitivity to apoptotic cell death as well as reduced caspase-3 and caspase-9 activation following exposure to staurosporine (STS) and C2-ceramide. L6 myoblasts with higher mitochondrial content also exhibited reduced apoptosis and AIF release following exposure to hydrogen peroxide (H2O2). Analysis of several key apoptosis regulatory proteins (ARC, Bax, Bcl-2, XIAP), antioxidant proteins (catalase, MnSOD, CuZnSOD), and reactive oxygen species (ROS) measures (DCF and MitoSOX fluorescence) revealed that these mechanisms were not responsible for the observed cellular protection. However, myoblasts with higher mitochondrial content were less sensitive to Ca(2+)-induced mitochondrial permeability transition pore formation (mPTP) and mitochondrial membrane depolarization. Collectively, these data demonstrate that increased mitochondrial content at physiological levels provides protection against apoptotic cell death by decreasing caspase-dependent and caspase-independent signaling through influencing mitochondrial Ca(2+)-mediated apoptotic events. Therefore, increasing mitochondrial biogenesis/content may represent a potential therapeutic approach in skeletal muscle disorders displaying increased apoptosis. PMID:23643731

Dam, Aaron D; Mitchell, Andrew S; Quadrilatero, Joe

2013-12-01

106

A heme-sensing mechanism in the translational regulation of mitochondrial cytochrome c oxidase biogenesis.  

PubMed

Heme plays fundamental roles as cofactor and signaling molecule in multiple pathways devoted to oxygen sensing and utilization in aerobic organisms. For cellular respiration, heme serves as a prosthetic group in electron transfer proteins and redox enzymes. Here we report that in the yeast Saccharomyces cerevisiae, a heme-sensing mechanism translationally controls the biogenesis of cytochrome c oxidase (COX), the terminal mitochondrial respiratory chain enzyme. We show that Mss51, a COX1 mRNA-specific translational activator and Cox1 chaperone, which coordinates Cox1 synthesis in mitoribosomes with its assembly in COX, is a heme-binding protein. Mss51 contains two heme regulatory motifs or Cys-Pro-X domains located in its N terminus. Using a combination of in vitro and in vivo approaches, we have demonstrated that these motifs are important for heme binding and efficient performance of Mss51 functions. We conclude that heme sensing by Mss51 regulates COX biogenesis and aerobic energy production. PMID:23217259

Soto, Iliana C; Fontanesi, Flavia; Myers, Richard S; Hamel, Patrice; Barrientos, Antoni

2012-12-01

107

The Interplay Between Apoptosis, Mitophagy and Mitochondrial Biogenesis Induced by Resveratrol Can Determine Activated Hepatic Stellate Cells Death or Survival.  

PubMed

Resveratrol has been the focus of numerous studies reporting opposite effects that depend on its concentration. The GRX is an activated hepatic stellate cells model used to study liver fibrosis development and resolution. We recently showed that GRX treatment with RSV (0.1-50 µM) for 24 h triggered dose-dependent pro-oxidant effects, resulting in cytotoxicity and cell damage only at the highest concentration. Here, we evaluated whether the pro-oxidant effect of resveratrol treatment is accompanied by alterations on the GRX mitochondrial metabolism, and whether the concomitantly autophagy/mitophagy induction can influence on cell death or survival. We demonstrated that all concentrations of resveratrol promoted an increase of GRX cell death signals, altering the mitochondrial dynamics and function. Cells treated with all resveratrol concentrations presented higher autophagy/mitophagy features, but only treatments with 1 and 10 µM of resveratrol-induced mitochondrial biogenesis. Since cell damage was higher and there was no mitochondrial biogenesis in GRX treated with 50 µM of resveratrol, we suggest that these cells failed to remove and replace all damaged mitochondria. In conclusion, the cytotoxic effect of resveratrol that effectively promotes cell death could be related to the interrelation between the concomitant induction of apoptosis, autophagy/mitophagy and mitochondrial biogenesis in GRX. PMID:25234614

Meira Martins, Leo A; Vieira, Moema Queiroz; Ilha, Mariana; de Vasconcelos, Mariana; Biehl, Henrique B; Lima, Daniela B; Schein, Vanessa; Barbé-Tuana, Florencia; Borojevic, Radovan; Guma, Fátima Costa Rodrigues

2014-09-19

108

The combination of oral quercetin supplementation and exercise prevents brain mitochondrial biogenesis.  

PubMed

The purpose of this study was to investigate whether the combination of oral quercetin (Q) supplementation and exercise prevents mitochondrial biogenesis. Four groups of Wistar rats were tested: quercetin-sedentary (Q-sedentary); quercetin-exercised (Q-exercised); no-quercetin-sedentary (NQ-sedentary); and no-quercetin-exercised (NQ-exercised). Treadmill exercise training took place 5 days a week for 6 weeks. Quercetin groups were supplemented with 25 mg/kg of quercetin throughout the experimental period. Sirtuin 1 (SIRT1), peroxisome-proliferator-activated receptor ? coactivator-1? (PGC-1?) mRNA levels and the activity of citrate synthase (CS) were measured in the brain. Redox status was also quantified by measuring the enzymatic activity of catalase (CAT) and superoxide dismutase (SOD) and protein carbonyls content (PCC). Q-Exercised (P < 0.001) and Q-sedentary (P = 0.042) groups increased PCC. In the Q-sedentary, there was an antioxidant enzymatic activity modulation for CAT (P < 0.001) and SOD (P < 0.01) but not in the Q-exercised. Q-sedentary showed a similar response to exercise in the brain by increasing CS activity in the brain (P < 0.01) and by activating the transcription of SIRT1 (P < 0.001) and PGC-1? (P = 0.03). These effects were hampered in the Q-exercised group. Quercetin is a pro-oxidant agent in the brain, but it modulates antioxidant activity in a sedentary condition. Quercetin supplementation during exercise compromises mitochondrial biogenesis induced separately by quercetin and exercise. PMID:25091043

Casuso, Rafael Antonio; Martínez-López, Emilio José; Hita-Contreras, Fidel; Camiletti-Moiron, Daniel; Martínez-Romero, Rubén; Cañuelo, Ana; Martínez-Amat, Antonio

2014-09-01

109

Increased mitochondrial biogenesis preserves intestinal stem cell homeostasis and contributes to longevity in Indy mutant flies.  

PubMed

The Drosophila Indy (I'm Not Dead Yet) gene encodes a plasma membrane transporter of Krebs cycle intermediates, with robust expression in tissues associated with metabolism. Reduced INDY alters metabolism and extends longevity in a manner similar to caloric restriction (CR); however, little is known about the tissue specific physiological effects of INDY reduction. Here we focused on the effects of INDY reduction in the Drosophila midgut due to the importance of intestinal tissue homeostasis in healthy aging and longevity. The expression of Indy mRNA in the midgut changes in response to aging and nutrition. Genetic reduction of Indy expression increases midgut expression of the mitochondrial regulator spargel/dPGC-1, which is accompanied by increased mitochondrial biogenesis and reduced reactive oxygen species (ROS). These physiological changes in the Indy mutant midgut preserve intestinal stem cell (ISC) homeostasis and are associated with healthy aging. Genetic studies confirm that dPGC-1 mediates the regulatory effects of INDY, as illustrated by lack of longevity extension and ISC homeostasis in flies with mutations in both Indy and dPGC1. Our data suggest INDY may be a physiological regulator that modulates intermediary metabolism in response to changes in nutrient availability and organismal needs by modulating dPGC-1. PMID:24827528

Rogers, Ryan P; Rogina, Blanka

2014-04-01

110

Transducer of regulated CREB-binding proteins (TORCs) induce PGC1 transcription and mitochondrial biogenesis in muscle cells  

Microsoft Academic Search

PGC-1 (peroxisome proliferator-activated receptor coactivator 1) is a master regulator of mitochondrial biogenesis and plays an important role in several other aspects of energy metabolism. To identify upstream regulators of PGC-1 gene transcription, 10,000 human full-length cDNAs were screened for induction of the PGC-1 promoter. A number of activators of PGC-1 transcription were found; the most potent activator was the

Zhidan Wu; Xueming Huang; Yajun Feng; Christoph Handschin; Yan Feng; P. Scott Gullicksen; Olivia Bare; Mark Labow; Bruce Spiegelman; Susan C. Stevenson

2006-01-01

111

Impaired mitochondrial biogenesis contributes to depletion of functional mitochondria in chronic MPP+ toxicity: dual roles for ERK1/2  

PubMed Central

The regulation of mitochondrial quality has emerged as a central issue in neurodegeneration, diabetes, and cancer. We utilized repeated low-dose applications of the complex I inhibitor 1-methyl-4-phenylpyridinium (MPP+) over 2 weeks to study cellular responses to chronic mitochondrial stress. Chronic MPP+ triggered depletion of functional mitochondria resulting in diminished capacities for aerobic respiration. Inhibiting autophagy/mitophagy only partially restored mitochondrial content. In contrast, inhibiting activation of extracellular signal-regulated protein kinases conferred complete cytoprotection with full restoration of mitochondrial functional and morphological parameters, enhancing spare respiratory capacity in MPP+ co-treated cells above that of control cells. Reversal of mitochondrial injury occurred when U0126 was added 1 week after MPP+, implicating enhanced repair mechanisms. Chronic MPP+ caused a >90% decrease in complex I subunits, along with decreases in complex III and IV subunits. Decreases in respiratory complex subunits were reversed by co-treatment with U0126, ERK1/2 RNAi or transfection of dominant-negative MEK1, but only partially restored by degradation inhibitors. Chronic MPP+ also suppressed the de novo synthesis of mitochondrial DNA-encoded proteins, accompanied by decreased expression of the mitochondrial transcription factor TFAM. U0126 completely reversed each of these deficits in mitochondrial translation and protein expression. These data indicate a key, limiting role for mitochondrial biogenesis in determining the outcome of injuries associated with elevated mitophagy. PMID:22622131

Zhu, J H; Gusdon, A M; Cimen, H; Van Houten, B; Koc, E; Chu, C T

2012-01-01

112

Testosterone Plus Low-Intensity Physical Training in Late Life Improves Functional Performance, Skeletal Muscle Mitochondrial Biogenesis, and Mitochondrial Quality Control in Male Mice  

PubMed Central

Testosterone supplementation increases muscle mass in older men but has not been shown to consistently improve physical function and activity. It has been hypothesized that physical exercise is required to induce the adaptations necessary for translation of testosterone-induced muscle mass gain into functional improvements. However, the effects of testosterone plus low intensity physical exercise training (T/PT) on functional performance and bioenergetics are unknown. In this pilot study, we tested the hypothesis that combined administration of T/PT would improve functional performance and bioenergetics in male mice late in life more than low-intensity physical training alone. 28-month old male mice were randomized to receive T/PT or vehicle plus physical training (V/PT) for 2 months. Compare to V/PT control, administration of T/PT was associated with improvements in muscle mass, grip strength, spontaneous physical movements, and respiratory activity. These changes were correlated with increased mitochondrial DNA copy number and expression of markers for mitochondrial biogenesis. Mice receiving T/PT also displayed increased expression of key elements for mitochondrial quality control, including markers for mitochondrial fission-and-fusion and mitophagy. Concurrently, mice receiving T/PT also displayed increased expression of markers for reduced tissue oxidative damage and improved muscle quality. Conclusion: Testosterone administered with low-intensity physical training improves grip strength, spontaneous movements, and respiratory activity. These functional improvements were associated with increased muscle mitochondrial biogenesis and improved mitochondrial quality control. PMID:23240002

Guo, Wen; Wong, Siu; Li, Michelle; Liang, Wentao; Liesa, Marc; Serra, Carlo; Jasuja, Ravi; Bartke, Andrzej; Kirkland, James L.; Shirihai, Orian; Bhasin, Shalender

2012-01-01

113

Exercise induces transient transcriptional activation of the PGC-1? gene in human skeletal muscle  

PubMed Central

Endurance exercise training induces mitochondrial biogenesis in skeletal muscle. The peroxisome proliferator activated receptor co-activator 1? (PGC-1?) has recently been identified as a nuclear factor critical for coordinating the activation of genes required for mitochondrial biogenesis in cell culture and rodent skeletal muscle. To determine whether PGC-1? transcription is regulated by acute exercise and exercise training in human skeletal muscle, seven male subjects performed 4 weeks of one-legged knee extensor exercise training. At the end of training, subjects completed 3 h of two-legged knee extensor exercise. Biopsies were obtained from the vastus lateralis muscle of both the untrained and trained legs before exercise and after 0, 2, 6 and 24 h of recovery. Time to exhaustion (2 min maximum resistance), as well as hexokinase II (HKII), citrate synthase and 3-hydroxyacyl-CoA dehydrogenase mRNA, were higher in the trained than the untrained leg prior to exercise. Exercise induced a marked transient increase (P < 0.05) in PGC-1? transcription (10- to > 40-fold) and mRNA content (7- to 10-fold), peaking within 2 h after exercise. Activation of PGC-1? was greater in the trained leg despite the lower relative workload. Interestingly, exercise did not affect nuclear respiratory factor 1 (NRF-1) mRNA, a gene induced by PGC-1? in cell culture. HKII, mitochondrial transcription factor A, peroxisome proliferator activated receptor ?, and calcineurin A? and A? mRNA were elevated (?2- to 6-fold; P < 0.05) at 6 h of recovery in the untrained leg but did not change in the trained leg. The present data demonstrate that exercise induces a dramatic transient increase in PGC-1? transcription and mRNA content in human skeletal muscle. Consistent with its role as a transcriptional coactivator, these findings suggest that PGC-1? may coordinate the activation of metabolic genes in human muscle in response to exercise. PMID:12563009

Pilegaard, Henriette; Saltin, Bengt; Neufer, P Darrell

2003-01-01

114

Erythropoietin enhances mitochondrial biogenesis in cardiomyocytes exposed to chronic hypoxia through Akt/eNOS signalling pathway.  

PubMed

Adaptation of cardiomyocytes to chronic hypoxia in cyanotic patients remains unclear. Mitochondrial biogenesis is enhanced in myocardium from cyanotic patients, which is possibly an adaptive response. Erythropoietin (EPO) in blood and its receptor (EPOR) on cardiomyocytes are upregulated by chronic hypoxia, suggesting that EPO-EPOR interaction is increased, which is inferred to positively regulate mitochondrial biogenesis through protein kinase B (Akt)/endothelial nitric oxide synthase (eNOS) signalling pathway. H9c2 cardiomyocytes were exposed to hypoxia (1% O(2)) for 1 week and treated with different doses of recombinant human erythropoietin (rhEPO). Mitochondrial number, mitochondrial DNA (mtDNA) copy number and peroxisome proliferator activated receptor gamma coactivator alpha (PGC-1?) mRNA expression increased in a dose-dependent manner induced by rhEPO. Akt and eNOS were significantly phosphorylated by rhEPO. Both blocking Akt with Wortmannin and silencing eNOS expression with shRNA plasmid decreased the mtDNA copy number and PGC-1? mRNA expression induced by rhEPO. Blocking Akt was associated with the decreased phosphorylation of Akt and eNOS. RNA interference led to a reduction in the total and phosphorylated proteins of eNOS. Thus EPO enhances mitochondrial biogenesis in cardiomyocytes exposed to chronic hypoxia, at least partly through Akt/eNOS signalling, which might be an adaptive mechanism of cardiomyocytes associated with the increased EPO-EPOR interaction in patients with cyanotic congenital heart disease (CCHD). PMID:24436050

Qin, Chuan; Zhou, Shengkai; Xiao, Yingbin; Chen, Lin

2014-03-01

115

Role of Phosphatidylethanolamine in the Biogenesis of Mitochondrial Outer Membrane Proteins*  

PubMed Central

The mitochondrial outer membrane contains proteinaceous machineries for the import and assembly of proteins, including TOM (translocase of the outer membrane) and SAM (sorting and assembly machinery). It has been shown that the dimeric phospholipid cardiolipin is required for the stability of TOM and SAM complexes and thus for the efficient import and assembly of ?-barrel proteins and some ?-helical proteins of the outer membrane. Here, we report that mitochondria deficient in phosphatidylethanolamine (PE), the second non-bilayer-forming phospholipid, are impaired in the biogenesis of ?-barrel proteins, but not of ?-helical outer membrane proteins. The stability of TOM and SAM complexes is not disturbed by the lack of PE. By dissecting the import steps of ?-barrel proteins, we show that an early import stage involving translocation through the TOM complex is affected. In PE-depleted mitochondria, the TOM complex binds precursor proteins with reduced efficiency. We conclude that PE is required for the proper function of the TOM complex. PMID:23625917

Becker, Thomas; Horvath, Susanne E.; Böttinger, Lena; Gebert, Natalia; Daum, Günther; Pfanner, Nikolaus

2013-01-01

116

Differential Expression of PGC-1? and Metabolic Sensors Suggest Age-Dependent Induction of Mitochondrial Biogenesis in Friedreich Ataxia Fibroblasts  

PubMed Central

Background Friedreich's ataxia (FRDA) is a mitochondrial rare disease, which molecular origin is associated with defect in the expression of frataxin. The pathological consequences are degeneration of nervous system structures and cardiomyopathy with necrosis and fibrosis, among others. Principal Findings Using FRDA fibroblasts we have characterized the oxidative stress status and mitochondrial biogenesis. We observed deficiency of MnSOD, increased ROS levels and low levels of ATP. Expression of PGC-1? and mtTFA was increased and the active form of the upstream signals p38 MAPK and AMPK in fibroblasts from two patients. Interestingly, the expression of energetic factors correlated with the natural history of disease of the patients, the age when skin biopsy was performed and the size of the GAA expanded alleles. Furthermore, idebenone inhibit mitochondriogenic responses in FRDA cells. Conclusions The induction of mitochondrial biogenesis in FRDA may be a consequence of the mitochondrial impairment associated with disease evolution. The increase of ROS and the involvement of the oxidative phosphorylation may be an early event in the cell pathophysiology of frataxin deficiency, whereas increase of mitochondriogenic response might be a later phenomenon associated to the individual age and natural history of the disease, being more evident as the patient age increases and disease evolves. This is a possible explanation of heart disease in FRDA. PMID:21687738

García-Giménez, José Luis; Gimeno, Amparo; Gonzalez-Cabo, Pilar; Dasí, Francisco; Bolinches-Amorós, Arantxa; Mollá, Belén; Palau, Francesc; Pallardó, Federico V.

2011-01-01

117

Enhanced oxidative stress and aberrant mitochondrial biogenesis in human neuroblastoma SH-SY5Y cells during methamphetamine induced apoptosis  

SciTech Connect

Methamphetamine (METH) is an abused drug that may cause psychiatric and neurotoxic damage, including degeneration of monoaminergic terminals and apoptosis of non-monoaminergic cells in Brain. The cellular and molecular mechanisms underlying these METH-induced neurotoxic effects remain to be clarified. In this study, we performed a time course assessment to investigate the effects of METH on intracellular oxidative stress and mitochondrial alterations in a human dopaminergic neuroblastoma SH-SY5Y cell line. We characterized that METH induces a temporal sequence of several cellular events including, firstly, a decrease in mitochondrial membrane potential within 1 h of the METH treatment, secondly, an extensive decline in mitochondrial membrane potential and increase in the level of reactive oxygen species (ROS) after 8 h of the treatment, thirdly, an increase in mitochondrial mass after the drug treatment for 24 h, and finally, a decrease in mtDNA copy number and mitochondrial proteins per mitochondrion as well as the occurrence of apoptosis after 48 h of the treatment. Importantly, vitamin E attenuated the METH-induced increases in intracellular ROS level and mitochondrial mass, and prevented METH-induced cell death. Our observations suggest that enhanced oxidative stress and aberrant mitochondrial biogenesis may play critical roles in METH-induced neurotoxic effects.

Wu, C.-W. [Department and Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei, Taiwan 112 (China); Ping, Y.-H. [Department and Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei, Taiwan 112 (China); Department of Education and Research, Taipei City Hospital, Taipei, Taiwan (China); Brain Research Center, University System of Taiwan, Taiwan (China); Yen, J.-C. [Department and Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei, Taiwan 112 (China); Department of Education and Research, Taipei City Hospital, Taipei, Taiwan (China); Brain Research Center, University System of Taiwan, Taiwan (China); Chang, C.-Y. [Department and Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei, Taiwan 112 (China); Wang, S.-F. [Department and Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei, Taiwan 112 (China); Yeh, C.-L. [Department and Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei, Taiwan 112 (China); Chi, C.-W. [Department a nd Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei, Taiwan 112 (China); Department of Medical Research and Education, Taipei Veterans General Hospital, Taiwan 112 (China); Lee, H.-C. [Department and Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei, Taiwan 112 (China) and Department of Education and Research, Taipei City Hospital, Taipei, Taiwan (China) and Brain Research Center, University System of Taiwan, Taiwan (China)]. E-mail: hclee2@ym.edu.tw

2007-05-01

118

Melatonin Improves mitochondrial function by promoting MT1/SIRT1/PGC-1 alpha-dependent mitochondrial biogenesis in cadmium-induced hepatotoxicity in vitro.  

PubMed

Melatonin is an indolamine synthesized in the pineal gland that has a wide range of physiological functions, and it has been under clinical investigation for expanded applications. Increasing evidence demonstrates that melatonin can ameliorate cadmium-induced hepatotoxicity. However, the potentially protective effects of melatonin against cadmium-induced hepatotoxicity and the underlying mechanisms of this protection remain unclear. This study investigates the protective effects of melatonin pretreatment on cadmium-induced hepatotoxicity and elucidates the potential mechanism of melatonin-mediated protection. We exposed HepG2 cells to different concentrations of cadmium chloride (2.5, 5, and 10 ?M) for 12 h. We found that Cd stimulated cytotoxicity, disrupted the mitochondrial membrane potential, increased reactive oxygen species production, and decreased mitochondrial mass and mitochondrial DNA content. Consistent with this finding, Cd exposure was associated with decreased Sirtuin 1 (SIRT1) protein expression and activity, thus promoted acetylation of PGC-1 alpha, a key enzyme involved in mitochondrial biogenesis and function, although Cd did not disrupt the interaction between SIRT1 and PGC-1 alpha. However, all cadmium-induced mitochondrial oxidative injuries were efficiently attenuated by melatonin pretreatment. Moreover, Sirtinol and SIRT1 siRNA each blocked the melatonin-mediated elevation in mitochondrial function by inhibiting SIRT1/ PGC-1 alpha signaling. Luzindole, a melatonin receptor antagonist, was found to partially block the ability of melatonin to promote SIRT1/ PGC-1 alpha signaling. In summary, our results indicate that SIRT1 plays an essential role in the ability of moderate melatonin to stimulate PGC-1 alpha and improve mitochondrial biogenesis and function at least partially through melatonin receptors in cadmium-induced hepatotoxicity. PMID:25159133

Guo, Pan; Pi, Huifeng; Xu, Shangcheng; Zhang, Lei; Li, Yuming; Li, Min; Cao, Zhengwang; Tian, Li; Xie, Jia; Li, Renyan; He, Mindi; Lu, Yonghui; Liu, Chuan; Duan, Weixia; Yu, Zhengping; Zhou, Zhou

2014-11-01

119

Chromosomal localization of mitochondrial transcription factor A (TCF6), single-stranded DNA-binding protein (SSBP), and Endonuclease G (ENDOG), three human housekeeping genes involved in mitochondrial biogenesis  

Microsoft Academic Search

By using a PCR-based screening of a somatic cell hybrid panel and FISH, we have assigned the loci of mitochondrial single-stranded DNA-binding protein (SSBP), mitochondrial transcription factor A (TCF6), and mitochondrial endonuclease G (ENDOG) genes to human chromosomes 7q34, 10q21, and 9q34.1, respectively. The products of these three genes are involved in fundamental aspects of mitochondrial biogenesis, such as replication

Valeria Tiranti; Elena Rossi; Adolf Ruiz-Carrillo; Giacomina Rossi; Mariano Rocchi; Stefano Didonato; Orsetta Zuffardi; Massimo Zeviani

1995-01-01

120

?-Lipoic acid treatment increases mitochondrial biogenesis and promotes beige adipose features in subcutaneous adipocytes from overweight/obese subjects.  

PubMed

?-Lipoic acid (?-Lip) is a natural occurring antioxidant with beneficial anti-obesity properties. The aim of this study was to investigate the putative effects of ?-Lip on mitochondrial biogenesis and the acquirement of brown-like characteristics by subcutaneous adipocytes from overweight/obese subjects. Thus, fully differentiated human subcutaneous adipocytes were treated with ?-Lip (100 and 250?M) for 24h for studies on mitochondrial content and morphology, mitochondrial DNA (mtDNA) copy number, fatty acid oxidation enzymes and brown/beige characteristic genes. The involvement of the Sirtuin1/Peroxisome proliferator-activated receptor gamma, coactivator 1 alpha (SIRT1/PGC-1?) pathway was also evaluated. Our results showed that ?-Lip increased mitochondrial content in cultured human adipocytes as revealed by electron microscopy and by mitotracker green labeling. Moreover, an enhancement in mtDNA content was observed. This increase was accompanied by an up-regulation of SIRT1 protein levels, a decrease in PGC-1? acetylation and up-regulation of Nuclear respiratory factor 1 (Nrf1) and Mitochondrial transcription factor (Tfam) transcription factors. Enhanced oxygen consumption and fatty acid oxidation enzymes, Carnitine palmitoyl transferase 1 and Acyl-coenzyme A oxidase (CPT-1 and ACOX) were also observed. Mitochondria from ?-Lip-treated adipocytes exhibited some morphological characteristics of brown mitochondria, and ?-Lip also induced up-regulation of some brown/beige adipocytes markers such as cell death-inducing DFFA-like effector a (Cidea) and T-box 1 (Tbx1). Moreover, ?-Lip up-regulated PR domain containing 16 (Prdm16) mRNA levels in treated adipocytes. Therefore, our study suggests the ability of ?-Lip to promote mitochondrial biogenesis and brown-like remodeling in cultured white subcutaneous adipocytes from overweight/obese donors. PMID:25542506

Fernández-Galilea, Marta; Pérez-Matute, Patricia; Prieto-Hontoria, Pedro L; Houssier, Marianne; Burrell, María A; Langin, Dominique; Martínez, J Alfredo; Moreno-Aliaga, María J

2015-03-01

121

[Exercise-induced asthma].  

PubMed

Exercise-induced asthma is characterized by a transient rise of the airways resistances, associated with asthmatic symptoms, 5 to 10 minutes after the end of a submaximal effort. The treatment is based on a pre-effort warming, cover the mouth with a mask (when the weather is cold), the use of beta-mimetic bronchodilators before exercise and, chronic treatment with antiinflammatory drugs. When the patient is not controlled, an evaluation of the lung function is required with a postbronchodilator control or an exercise challenge test. If the patient remains uncontrolled despite the treatment, others diagnostics should be excluded, such as vocal cords dysfunction or left heart failure. PMID:21089401

Michel, O

2010-09-01

122

Exercise-Induced Neuroprotection of Hippocampus in APP/PS1 Transgenic Mice via Upregulation of Mitochondrial 8-Oxoguanine DNA Glycosylase  

PubMed Central

Improving mitochondrial function has been proposed as a reasonable therapeutic strategy to reduce amyloid-? (A?) load and to modify the progression of Alzheimer's disease (AD). However, the relationship between mitochondrial adaptation and brain neuroprotection caused by physical exercise in AD is poorly understood. This study was undertaken to investigate the effects of long-term treadmill exercise on mitochondrial 8-oxoguanine DNA glycosylase-1 (OGG1) level, mtDNA oxidative damage, and mitochondrial function in the hippocampus of APP/PS1 transgenic mouse model of AD. In the present study, twenty weeks of treadmill training significantly improved the cognitive function and reduced the expression of A?-42 in APP/PS1 transgenic (Tg) mice. Training also ameliorated mitochondrial respiratory function by increasing the complexes I, and IV and ATP synthase activities, whereas it attenuated ROS generation and mtDNA oxidative damage in Tg mice. Furthermore, the impaired mitochondrial antioxidant enzymes and mitochondrial OGG1 activities seen in Tg mice were restored with training. Acetylation level of mitochondrial OGG1 and MnSOD was markedly suppressed in Tg mice after exercise training, in parallel with increased level of SIRT3. These findings suggest that exercise training could increase mtDNA repair capacity in the mouse hippocampus, which in turn would result in protection against AD-related mitochondrial dysfunction and phenotypic deterioration. PMID:25538817

Kang, Weimin; Jiang, Ning; Wang, Xun; Zhang, Yong; Ji, Li Li

2014-01-01

123

Regulation of Mitochondrial Biogenesis by Lipoprotein Lipase in Muscle of Insulin-Resistant Offspring of Parents With Type 2 Diabetes  

PubMed Central

Recent studies reveal a strong relationship between reduced mitochondrial content and insulin resistance in human skeletal muscle, although the underlying factors responsible for this association remain unknown. To address this question, we analyzed muscle biopsy samples from young, lean, insulin resistant (IR) offspring of parents with type 2 diabetes and control subjects by microarray analyses and found significant differences in expression of ?512 probe pairs. We then screened these genes for their potential involvement in the regulation of mitochondrial biogenesis using RNA interference and found that mRNA and protein expression of lipoprotein lipase (LPL) in skeletal muscle was significantly decreased in the IR offspring and was associated with decreased mitochondrial density. Furthermore, we show that LPL knockdown in muscle cells decreased mitochondrial content by effectively decreasing fatty acid delivery and subsequent activation of peroxisome proliferator–activated receptor (PPAR)-?. Taken together, these data suggest that decreased mitochondrial content in muscle of IR offspring may be due in part to reductions in LPL expression in skeletal muscle resulting in decreased PPAR-? activation. PMID:22368174

Morino, Katsutaro; Petersen, Kitt Falk; Sono, Saki; Choi, Cheol Soo; Samuel, Varman T.; Lin, Aiping; Gallo, Amy; Zhao, Hongyu; Kashiwagi, Atsunori; Goldberg, Ira J.; Wang, Hong; Eckel, Robert H.; Maegawa, Hiroshi; Shulman, Gerald I.

2012-01-01

124

The neurogenic basic helix-loop-helix transcription factor NeuroD6 enhances mitochondrial biogenesis and bioenergetics to confer tolerance of neuronal PC12-NeuroD6 cells to the mitochondrial stressor rotenone  

SciTech Connect

The fundamental question of how and which neuronal specific transcription factors tailor mitochondrial biogenesis and bioenergetics to the need of developing neuronal cells has remained largely unexplored. In this study, we report that the neurogenic basic helix-loop-helix transcription factor NeuroD6 possesses mitochondrial biogenic properties by amplifying the mitochondrial DNA content and TFAM expression levels, a key regulator for mitochondrial biogenesis. NeuroD6-mediated increase in mitochondrial biogenesis in the neuronal progenitor-like PC12-NEUROD6 cells is concomitant with enhanced mitochondrial bioenergetic functions, including increased expression levels of specific subunits of respiratory complexes of the electron transport chain, elevated mitochondrial membrane potential and ATP levels produced by oxidative phosphorylation. Thus, NeuroD6 augments the bioenergetic capacity of PC12-NEUROD6 cells to generate an energetic reserve, which confers tolerance to the mitochondrial stressor, rotenone. We found that NeuroD6 induces an adaptive bioenergetic response throughout rotenone treatment involving maintenance of the mitochondrial membrane potential and ATP levels in conjunction with preservation of the actin network. In conclusion, our results support the concept that NeuroD6 plays an integrative role in regulating and coordinating the onset of neuronal differentiation with acquisition of adequate mitochondrial mass and energetic capacity to ensure energy demanding events, such as cytoskeletal remodeling, plasmalemmal expansion, and growth cone formation. -- Highlights: Black-Right-Pointing-Pointer NeuroD6 induces mitochondrial biogenesis in neuroprogenitor-like cells. Black-Right-Pointing-Pointer NeuroD6 augments the bioenergetic reserve of the neuronal PC12-NeuroD6 cells. Black-Right-Pointing-Pointer NeuroD6 increases the mitochondrial membrane potential and ATP levels. Black-Right-Pointing-Pointer NeuroD6 confers tolerance to rotenone via an adaptive mitochondrial response.

Baxter, Kristin Kathleen; Uittenbogaard, Martine [Department of Anatomy and Regenerative Biology, George Washington University Medical Center, Washington, DC (United States)] [Department of Anatomy and Regenerative Biology, George Washington University Medical Center, Washington, DC (United States); Chiaramello, Anne, E-mail: achiaram@gwu.edu [Department of Anatomy and Regenerative Biology, George Washington University Medical Center, Washington, DC (United States)] [Department of Anatomy and Regenerative Biology, George Washington University Medical Center, Washington, DC (United States)

2012-10-15

125

Mitochondrial DNA (mtDNA) Biogenesis: Visualization and Duel Incorporation of BrdU and EdU Into Newly Synthesized mtDNA In Vitro  

PubMed Central

Mitochondria are key regulators of cellular energy and are the focus of a large number of studies examining the regulation of mitochondrial dynamics and biogenesis in healthy and diseased conditions. One approach to monitoring mitochondrial biogenesis is to measure the rate of mitochondrial DNA (mtDNA) replication. We developed a sensitive technique to visualize newly synthesized mtDNA in individual cells to study mtDNA replication within subcellular compartments of neurons. The technique combines the incorporation of 5-bromo-2-deoxyuridine (BrdU) and/or 5-ethynyl-2?-deoxyuridine (EdU) into mtDNA, together with a tyramide signal amplification protocol. Employing this technique, we visualized and measured mtDNA biogenesis in individual cells. The labeling procedure for EdU allows for more comprehensive results by allowing the comparison of its incorporation with other intracellular markers, because it does not require the harsh acid or enzyme digests necessary to recover the BrdU epitope. In addition, the utilization of both BrdU and EdU permits sequential pulse–chase experiments to follow the intracellular localization of mtDNA replication. The ability to quantify mitochondrial biogenesis provides an essential tool for investigating the alterations in mitochondrial dynamics involved in the pathogenesis of multiple cellular disorders, including neuropathies and neurodegenerative diseases. (J Histochem Cytochem 58:207–218, 2010) PMID:19875847

Lentz, Stephen I.; Edwards, James L.; Backus, Carey; McLean, Lisa L.; Haines, Kristine M.; Feldman, Eva L.

2010-01-01

126

Induction of mitochondrial biogenesis and respiration is associated with mTOR regulation in hepatocytes of rats treated with the pan-PPAR activator tetradecylthioacetic acid (TTA)  

SciTech Connect

Highlights: Black-Right-Pointing-Pointer We investigated mechanisms of mitochondrial regulation in rat hepatocytes. Black-Right-Pointing-Pointer Tetradecylthioacetic acid (TTA) was employed to activate mitochondrial oxidation. Black-Right-Pointing-Pointer Mitochondrial biogenesis and respiration were induced. Black-Right-Pointing-Pointer It was confirmed that PPAR target genes were induced. Black-Right-Pointing-Pointer The mechanism involved activation mTOR. -- Abstract: The hypolipidemic effect of peroxisome proliferator-activated receptor (PPAR) activators has been explained by increasing mitochondrial fatty acid oxidation, as observed in livers of rats treated with the pan-PPAR activator tetradecylthioacetic acid (TTA). PPAR-activation does, however, not fully explain the metabolic adaptations observed in hepatocytes after treatment with TTA. We therefore characterized the mitochondrial effects, and linked this to signalling by the metabolic sensor, the mammalian target of rapamycin (mTOR). In hepatocytes isolated from TTA-treated rats, the changes in cellular content and morphology were consistent with hypertrophy. This was associated with induction of multiple mitochondrial biomarkers, including mitochondrial DNA, citrate synthase and mRNAs of mitochondrial proteins. Transcription analysis further confirmed activation of PPAR{alpha}-associated genes, in addition to genes related to mitochondrial biogenesis and function. Analysis of mitochondrial respiration revealed that the capacity of both electron transport and oxidative phosphorylation were increased. These effects coincided with activation of the stress related factor, ERK1/2, and mTOR. The protein level and phosphorylation of the downstream mTOR actors eIF4G and 4E-BP1 were induced. In summary, TTA increases mitochondrial respiration by inducing hypertrophy and mitochondrial biogenesis in rat hepatocytes, via adaptive regulation of PPARs as well as mTOR.

Hagland, Hanne R.; Nilsson, Linn I.H. [Department of Biomedicine, University of Bergen (Norway)] [Department of Biomedicine, University of Bergen (Norway); Burri, Lena [Institute of Medicine, University of Bergen, Haukeland University Hospital (Norway)] [Institute of Medicine, University of Bergen, Haukeland University Hospital (Norway); Nikolaisen, Julie [Department of Biomedicine, University of Bergen (Norway)] [Department of Biomedicine, University of Bergen (Norway); Berge, Rolf K. [Institute of Medicine, University of Bergen, Haukeland University Hospital (Norway) [Institute of Medicine, University of Bergen, Haukeland University Hospital (Norway); Department of Heart Disease, Haukeland University Hospital (Norway); Tronstad, Karl J., E-mail: karl.tronstad@biomed.uib.no [Department of Biomedicine, University of Bergen (Norway)

2013-01-11

127

4-Hydroxyisoleucine improves insulin resistance by promoting mitochondrial biogenesis and act through AMPK and Akt dependent pathway.  

PubMed

4-Hydroxyisoleucine (4-HIL) is an unusual amino acid isolated from fenugreek seeds (Trigonella foenum graecum L). Various studies have shown that it acts as an antidiabetic agent yet its mechanism of action is not clear. We therefore investigated the effect 4-HIL on the high fructose diet fed streptozotocin induced diabetic rats and L6 myotubes. 4-HIL (50mg/kg) has improved blood lipid profile, glucose tolerance and insulin sensitivity in a diabetic rat model. It has increased the glucose uptake in L6 myotubes in AMPK-dependent manner and upregulated the expression of genes (PGC-1?, PGC-1?, CPT 1 and CPT 2), which have role in mitochondrial biogenesis and energy metabolism in the liver, skeletal muscles as well as in L6 myotubes. Interestingly, it also increased the AMPK and Akt expression along with their phosphorylated forms in the liver and muscle tissues of treated animals. Altogether we concluded that 4-HIL acts to improve insulin resistance by promoting mitochondrial biogenesis in high fructose diet fed STZ induced diabetic rats. PMID:25454462

Rawat, Arun Kumar; Korthikunta, Venkateswarlu; Gautam, Sudeep; Pal, Savita; Tadigoppula, Narender; Tamrakar, Akhilesh Kumar; Srivastava, Arvind Kumar

2014-12-01

128

Direct influence of the p53 tumor suppressor on mitochondrial biogenesis and function  

Microsoft Academic Search

Mitochondrial localization of p53 has been observed in several cell systems, but an under- standing of its organelle-based physiological activity remains incomplete. The purpose of the present study was to investigate the mitochondrial DNA genomic response to dominant-negative p53 mutant miniprotein (p53DD) fused to a mitochondrial import signal. Con- structs were generated to express mitochondrial tar- geted enhanced green fluorescent

RONALD J. DONAHUE; MARJANEH RAZMARA; JAN B. HOEK; THOMAS B. KNUDSEN

2001-01-01

129

Pioglitazone Induces Mitochondrial Biogenesis in Human Subcutaneous Adipose Tissue In Vivo  

Microsoft Academic Search

Thiazolidenediones such as pioglitazone improve insulin sensitivity in diabetic patients by several mechanisms, including increased uptake and metabolism of free fatty acids in adipose tissue. The purpose of the present study was to determine the effect of pioglitazone on mitochon- drial biogenesis and expression of genes involved in fatty acid oxidation in subcutaneous fat. Patients with type 2 diabetes were

Iwona Bogacka; Hui Xie; George A. Bray; Steven R. Smith

2005-01-01

130

Structure of dimeric mitochondrial ATP synthase: Novel F0 bridging features and the structural basis of mitochondrial cristae biogenesis  

Microsoft Academic Search

The F1F0-ATP synthase exists as a dimer in mitochondria, where it is essential for the biogenesis of the inner membrane cristae. How two ATP synthase complexes dimerize to promote cristae formation is unknown. Here we resolved the structure of the dimeric F1F0 ATP synthase complex isolated from bovine heart mitochondria by transmission electron microscopy. The structure of the ATP synthase

Fernando Minauro-Sanmiguel; Stephan Wilkens; José J. García

2005-01-01

131

The Neurogenic Basic Helix-Loop-Helix Transcription Factor NeuroD6 Enhances Mitochondrial Biogenesis and Bioenergetics to Confer Tolerance of Neuronal PC12-NeuroD6 Cells to the Mitochondrial Stressor Rotenone  

PubMed Central

The fundamental question of how and which neuronal specific transcription factors tailor mitochondrial bioenergetics to the need of developing neuronal cells has remained largely unexplored. In this study, we report that the neurogenic basic helix-loop-helix transcription factor NeuroD6 possesses mitochondrial biogenic properties by amplifying the mitochondrial DNA content and TFAM expression levels, a key regulator for mitochondrial biogenesis. NeuroD6-mediated increase in mitochondrial biogenesis in the neuronal progenitor-like PC12-NEUROD6 cells is concomitant with enhanced mitochondrial bioenergetic functions, including increased expression levels of specific subunits of respiratory complexes of the electron transport chain, elevated mitochondrial membrane potential and ATP levels produced by oxidative phosphorylation. Thus, NeuroD6 augments the bioenergetic capacity of PC12-NEUROD6 cells to generate an energetic reserve, which confers tolerance to the mitochondrial stressor, rotenone. We found that NeuroD6 induces an adaptive bioenergetic response throughout rotenone treatment involving maintenance of the mitochondrial membrane potential and ATP levels in conjunction with preservation of the actin network. In conclusion, our results support the concept that NeuroD6 plays an integrative role in regulating and coordinating the onset of neuronal differentiation with acquisition of adequate mitochondrial mass and energetic capacity to ensure energy demanding events, such as cytoskeletal remodeling, plasmalemmal expansion, and growth cone formation. PMID:22814253

Baxter, Kristin Kathleen; Uittenbogaard, Martine; Chiaramello, Anne

2012-01-01

132

Mitochondrial biogenesis and increased uncoupling protein 1 in brown adipose tissue of mice fed a ketone ester diet  

PubMed Central

We measured the effects of a diet in which d-?-hydroxybutyrate-(R)-1,3 butanediol monoester [ketone ester (KE)] replaced equicaloric amounts of carbohydrate on 8-wk-old male C57BL/6J mice. Diets contained equal amounts of fat, protein, and micronutrients. The KE group was fed ad libitum, whereas the control (Ctrl) mice were pair-fed to the KE group. Blood d-?-hydroxybutyrate levels in the KE group were 3-5 times those reported with high-fat ketogenic diets. Voluntary food intake was reduced dose dependently with the KE diet. Feeding the KE diet for up to 1 mo increased the number of mitochondria and doubled the electron transport chain proteins, uncoupling protein 1, and mitochondrial biogenesis-regulating proteins in the interscapular brown adipose tissue (IBAT). [18F]-Fluorodeoxyglucose uptake in IBAT of the KE group was twice that in IBAT of the Ctrl group. Plasma leptin levels of the KE group were more than 2-fold those of the Ctrl group and were associated with increased sympathetic nervous system activity to IBAT. The KE group exhibited 14% greater resting energy expenditure, but the total energy expenditure measured over a 24-h period or body weights was not different. The quantitative insulin-sensitivity check index was 73% higher in the KE group. These results identify KE as a potential antiobesity supplement.—Srivastava, S., Kashiwaya, Y., King, M. T. Baxa, U., Tam, J., Niu, G., Chen, X., Clarke, K., Veech, R. L. Mitochondrial biogenesis and increased uncoupling protein 1 in brown adipose tissue of mice fed a ketone ester diet. PMID:22362892

Srivastava, Shireesh; Kashiwaya, Yoshihiro; King, M. Todd; Baxa, Ulrich; Tam, Joseph; Niu, Gang; Chen, Xiaoyuan; Clarke, Kieran; Veech, Richard L.

2012-01-01

133

A switch in metabolism precedes increased mitochondrial biogenesis in respiratory chain-deficient mouse hearts  

Microsoft Academic Search

We performed global gene expression analyses in mouse hearts with progressive respiratory chain deficiency and found a metabolic switch at an early disease stage. The tissue-specific mitochondrial transcription factor A (Tfam) knockout mice of this study displayed a progressive heart phenotype with depletion of mtDNA and an accompanying severe decline of respiratory chain enzyme activities along with a decreased mitochondrial

Anna Hansson; Nicole Hance; Eric Dufour; Anja Rantanen; Kjell Hultenby; David A. Clayton; Rolf Wibom; Nils-Göran Larsson

2004-01-01

134

Agonism of the 5-Hydroxytryptamine 1F Receptor Promotes Mitochondrial Biogenesis and Recovery from Acute Kidney Injury  

PubMed Central

Many acute and chronic conditions, such as acute kidney injury, chronic kidney disease, heart failure, and liver disease, involve mitochondrial dysfunction. Although we have provided evidence that drug-induced stimulation of mitochondrial biogenesis (MB) accelerates mitochondrial and cellular repair, leading to recovery of organ function, only a limited number of chemicals have been identified that induce MB. The goal of this study was to assess the role of the 5-hydroxytryptamine 1F (5-HT1F) receptor in MB. Immunoblot and quantitative polymerase chain reaction analyses revealed 5-HT1F receptor expression in renal proximal tubule cells (RPTC). A MB screening assay demonstrated that two selective 5-HT1F receptor agonists, LY334370 (4-fluoro-N-[3-(1-methyl-4-piperidinyl)-1H-indol-5-yl]benzamide) and LY344864 (N-[(3R)-3-(dimethylamino)-2,3,4,9-tetrahydro-1H-carbazol-6-yl]-4-fluorobenzamide; 1–100 nM) increased carbonylcyanide-p-trifluoromethoxyphenylhydrazone–uncoupled oxygen consumption in RPTC, and validation studies confirmed both agonists increased mitochondrial proteins [e.g., ATP synthase ?, cytochrome c oxidase 1 (Cox1), and NADH dehydrogenase (ubiquinone) 1? subcomplex subunit 8 (NDUFB8)] in vitro. Small interfering RNA knockdown of the 5-HT1F receptor blocked agonist-induced MB. Furthermore, LY344864 increased peroxisome proliferator–activated receptor coactivator 1-?, Cox1, and NDUFB8 transcript levels and mitochondrial DNA (mtDNA) copy number in murine renal cortex, heart, and liver. Finally, LY344864 accelerated recovery of renal function, as indicated by decreased blood urea nitrogen and kidney injury molecule 1 and increased mtDNA copy number following ischemia/reperfusion-induced acute kidney injury (AKI). In summary, these studies reveal that the 5-HT1F receptor is linked to MB, 5-HT1F receptor agonism promotes MB in vitro and in vivo, and 5-HT1F receptor agonism promotes recovery from AKI injury. Induction of MB through 5-HT1F receptor agonism represents a new target and approach to treat mitochondrial organ dysfunction. PMID:24849926

Garrett, Sara M.; Whitaker, Ryan M.; Beeson, Craig C.

2014-01-01

135

Biogenesis of mitochondrial ?-barrel proteins: the POTRA domain is involved in precursor release from the SAM complex  

PubMed Central

The mitochondrial outer membrane contains proteinaceous machineries for the translocation of precursor proteins. The sorting and assembly machinery (SAM) is required for the insertion of ??barrel proteins into the outer membrane. Sam50 is the channel-forming core subunit of the SAM complex and belongs to the BamA/Sam50/Toc75 family of proteins that have been conserved from Gram-negative bacteria to mitochondria and chloroplasts. These proteins contain one or more N-terminal polypeptide transport-associated (POTRA) domains. POTRA domains can bind precursor proteins, however, different views exist on the role of POTRA domains in the biogenesis of ?-barrel proteins. It has been suggested that the single POTRA domain of mitochondrial Sam50 plays a receptor-like function at the SAM complex. We established a system to monitor the interaction of chemical amounts of ?-barrel precursor proteins with the SAM complex of wild-type and mutant yeast in organello. We report that the SAM complex lacking the POTRA domain of Sam50 efficiently binds ?-barrel precursors, but is impaired in the release of the precursors. These results indicate the POTRA domain of Sam50 is not essential for recognition of ?-barrel precursors but functions in a subsequent step to promote the release of precursor proteins from the SAM complex. PMID:21680715

Stroud, David A.; Becker, Thomas; Qiu, Jian; Stojanovski, Diana; Pfannschmidt, Sylvia; Wirth, Christophe; Hunte, Carola; Guiard, Bernard; Meisinger, Chris; Pfanner, Nikolaus; Wiedemann, Nils

2011-01-01

136

A subcomplex of human mitochondrial RNase P is a bifunctional methyltransferase—extensive moonlighting in mitochondrial tRNA biogenesis  

PubMed Central

Transfer RNAs (tRNAs) reach their mature functional form through several steps of processing and modification. Some nucleotide modifications affect the proper folding of tRNAs, and they are crucial in case of the non-canonically structured animal mitochondrial tRNAs, as exemplified by the apparently ubiquitous methylation of purines at position 9. Here, we show that a subcomplex of human mitochondrial RNase P, the endonuclease removing tRNA 5? extensions, is the methyltransferase responsible for m1G9 and m1A9 formation. The ability of the mitochondrial tRNA:m1R9 methyltransferase to modify both purines is uncommon among nucleic acid modification enzymes. In contrast to all the related methyltransferases, the human mitochondrial enzyme, moreover, requires a short-chain dehydrogenase as a partner protein. Human mitochondrial RNase P, thus, constitutes a multifunctional complex, whose subunits moonlight in cascade: a fatty and amino acid degradation enzyme in tRNA methylation and the methyltransferase, in turn, in tRNA 5? end processing. PMID:23042678

Vilardo, Elisa; Nachbagauer, Christa; Buzet, Aurélie; Taschner, Andreas; Holzmann, Johann; Rossmanith, Walter

2012-01-01

137

Biogenesis of mitochondria: the mitochondrial gene (aap1) coding for mitochondrial ATPase subunit 8 in Saccharomyces cerevisiae.  

PubMed Central

A mitochondrial gene (denoted aap1) in Saccharomyces cerevisiae has been characterized by nucleotide sequence analysis of a region of mtDNA between the oxi3 and oli2 genes. The reading frame of the aap1 gene specifies a hydrophobic polypeptide containing 48 amino acids. The functional nature of this reading frame was established by sequence analysis of a series of mit- mutants and revertants. Evidence is presented that the aap1 gene codes for a mitochondrially synthesized polypeptide associated with the mitochondrial ATPase complex. This polypeptide (denoted subunit 8) is a proteolipid whose size has been previously assumed to be 10 kilodaltons based on its mobility on SDS-polyacrylamide gels, but the sequence of the aap1 gene predicts a molecular weight of 5,815 for this protein. PMID:6223276

Macreadie, I G; Novitski, C E; Maxwell, R J; John, U; Ooi, B G; McMullen, G L; Lukins, H B; Linnane, A W; Nagley, P

1983-01-01

138

Chromosomal localization of mitochondrial transcription factor A (TCF6), single-stranded DNA-binding protein (SSBP), and endonuclease G (ENDOG), three human housekeeping genes involving in mitochondrial biogenesis  

SciTech Connect

By using a PCR-based screening of a somatic cell hybrid panel and FISH, we have assigned the loci of mitochondrial single-stranded DNA-binding protein (SSBP), mitochondrial transcription factor A (TCF6), and mitochondrial endonuclease G (ENDOG) genes to human chromosomes 7q34, 10q21, and 9q34.1, respectively. The products of these three genes are involved in fundamental aspects of mitochondrial biogenesis, such as replication and transcription of the mitochondrial genome. The chromosomal localization of these genes is important to testing whether the corresponding proteins may play a role in the etiopathogenesis of human disorders associated with qualitative or quantitative abnormalities of mitochondrial DNA. 20 refs., 1 fig., 2 tabs.

Tiranti, V.; Rossi, G.; DiDonato, S. [Istituto Nazionale Neurologico, Carlo Besta (Italy)] [and others] [Istituto Nazionale Neurologico, Carlo Besta (Italy); and others

1995-01-20

139

Cardiac-Specific Induction of the Transcriptional Coactivator Peroxisome Proliferator-Activated Receptor Coactivator1 Promotes Mitochondrial Biogenesis and Reversible Cardiomyopathy in a Developmental Stage-Dependent Manner  

Microsoft Academic Search

Recent evidence has identified the peroxisome proliferator-activated receptor coactivator-1 (PGC-1 )a s a regulator of cardiac energy metabolism and mitochondrial biogenesis. We describe the development of a transgenic system that permits inducible, cardiac-specific overexpression of PGC-1. Expression of the PGC-1 transgene in this system (tet-on PGC-1) is cardiac-specific in the presence of doxycycline (dox) and is not leaky in the

Laurie K. Russell; Carolyn M. Mansfield; John J. Lehman; Attila Kovacs; Michael Courtois; Jeffrey E. Saffitz; Denis M. Medeiros; Maria L. Valencik; John A. McDonald; Daniel P. Kelly

140

Genomic and non-genomic regulation of PGC1 isoforms by estrogen to increase cerebral vascular mitochondrial biogenesis and reactive oxygen species protection.  

PubMed

We previously found that estrogen exerts a novel protective effect on mitochondria in brain vasculature. Here we demonstrate in rat cerebral blood vessels that 17?-estradiol (estrogen), both in vivo and ex vivo, affects key transcriptional coactivators responsible for mitochondrial regulation. Treatment of ovariectomized rats with estrogen in vivo lowered mRNA levels of peroxisome proliferator-activated receptor-? coactivator-1 alpha (PGC-1?) but increased levels of the other PGC-1 isoforms: PGC-1? and PGC-1 related coactivator (PRC). In vessels ex vivo, estrogen decreased protein levels of PGC-1? via activation of phosphatidylinositol 3-kinase (PI3K). Estrogen treatment also increased phosphorylation of forkhead transcription factor, FoxO1, a known pathway for PGC-1? downregulation. In contrast to the decrease in PGC-1?, estrogen increased protein levels of nuclear respiratory factor 1, a known PGC target and mediator of mitochondrial biogenesis. The latter effect of estrogen was independent of PI3K, suggesting a separate mechanism consistent with increased expression of PGC-1? and PRC. We demonstrated increased mitochondrial biogenesis following estrogen treatment in vivo; cerebrovascular levels of mitochondrial transcription factor A and electron transport chain subunits as well as the mitochondrial/nuclear DNA ratio were increased. We examined a downstream target of PGC-1?, glutamate-cysteine ligase (GCL), the rate-limiting enzyme for glutathione synthesis. In vivo estrogen increased protein levels of both GCL subunits and total glutathione levels. Together these data show estrogen differentially regulates PGC-1 isoforms in brain vasculature, underscoring the importance of these coactivators in adapting mitochondria in specific tissues. By upregulating PGC-1? and/or PRC, estrogen appears to enhance mitochondrial biogenesis, function and reactive oxygen species protection. PMID:24275351

Kemper, Martin F; Stirone, Chris; Krause, Diana N; Duckles, Sue P; Procaccio, Vincent

2014-01-15

141

Green Tea Polyphenols Stimulate Mitochondrial Biogenesis and Improve Renal Function after Chronic Cyclosporin A Treatment in Rats  

PubMed Central

Our previous studies showed that an extract from Camellia sinenesis (green tea), which contains several polyphenols, attenuates nephrotoxicity caused by cyclosporine A (CsA). Since polyphenols are stimulators of mitochondrial biogenesis (MB), this study investigated whether stimulation of MB plays a role in green tea polyphenol protection against CsA renal toxicity. Rats were fed a powdered diet containing green tea polyphenolic extract (0.1%) starting 3 days prior to CsA treatment (25 mg/kg, i.g. daily for 3 weeks). CsA alone decreased renal nuclear DNA-encoded oxidative phosphorylation (OXPHOS) protein ATP synthase-? (AS-?) by 42%, mitochondrial DNA (mtDNA)-encoded OXPHOS protein NADH dehydrogenase-3 (ND3) by 87% and their associated mRNAs. Mitochondrial DNA copy number was also decreased by 78% by CsA. Immunohistochemical analysis showed decreased cytochrome c oxidase subunit IV (COX-IV), an OXPHOS protein, in tubular cells. Peroxisome proliferator-activated receptor-? coactivator (PGC)-1?, the master regulator of MB, and mitochondrial transcription factor-A (Tfam), the transcription factor that regulates mtDNA replication and transcription, were 42% and 90% lower, respectively, in the kidneys of CsA-treated than in untreated rats. These results indicate suppression of MB by chronic CsA treatment. Green tea polyphenols alone and following CsA increased AS-?, ND3, COX-IV, mtDNA copy number, PGC-1? mRNA and protein, decreased acetylated PGC-1?, and increased Tfam mRNA and protein. In association with suppressed MB, CsA increased serum creatinine, caused loss of brush border and dilatation of proximal tubules, tubular atrophy, vacuolization, apoptosis, calcification, and increased neutrophil gelatinase-associated lipocalin expression, leukocyte infiltration, and renal fibrosis. Green tea polyphenols markedly attenuated CsA-induced renal injury and improved renal function. Together, these results demonstrate that green tea polyphenols attenuate CsA-induced kidney injury, at least in part, through the stimulation of MB. PMID:23755172

Rehman, Hasibur; Krishnasamy, Yasodha; Haque, Khujista; Lemasters, John J.; Schnellmann, Rick G.; Zhong, Zhi

2013-01-01

142

Adolescents and Exercise Induced Asthma  

ERIC Educational Resources Information Center

This article defines asthma and exercise induced asthma, and provides information on the triggers, signs, and symptoms of an attack. It also gives treatments for these conditions, along with prevention guidelines on how to handle an attack in the classroom or on the practice field. (Contains 2 tables and 1 figure.)

Hansen, Pamela; Bickanse, Shanna; Bogenreif, Mike; VanSickle, Kyle

2008-01-01

143

The IMMUTANS variegation locus of Arabidopsis defines a mitochondrial alternative oxidase homolog that functions during early chloroplast biogenesis.  

PubMed Central

Nuclear gene-induced variegation mutants provide a powerful system to dissect interactions between the genetic systems of the nucleus-cytoplasm, the chloroplast, and the mitochondrion. The immutans (im) variegation mutation of Arabidopsis is nuclear and recessive and results in the production of green- and white-sectored leaves. The green sectors contain cells with normal chloroplasts, whereas the white sectors are heteroplastidic and contain cells with abnormal, pigment-deficient plastids as well as some normal chloroplasts. White sector formation can be promoted by enhanced light intensities, but sectoring becomes irreversible early in leaf development. The white sectors accumulate the carotenoid precursor phytoene. We have positionally cloned IM and found that the gene encodes a 40.5-kD protein with sequence motifs characteristic of alternative oxidase, a mitochondrial protein that functions as a terminal oxidase in the respiratory chains of all plants. However, phylogenetic analyses revealed that the IM protein is only distantly related to these other alternative oxidases, suggesting that IM is a novel member of this protein class. We sequenced three alleles of im, and all are predicted to be null. Our data suggest a model of variegation in which the IM protein functions early in chloroplast biogenesis as a component of a redox chain responsible for phytoene desaturation but that a redundant electron transfer function is capable of compensating for IM activity in some plastids and cells. PMID:9878631

Wu, D; Wright, D A; Wetzel, C; Voytas, D F; Rodermel, S

1999-01-01

144

The novel nuclear gene DSS1 of Saccharomyces cerevisiae is necessary for mitochondrial biogenesis  

Microsoft Academic Search

A previously unknown nuclear gene DSS-1 from Saccharomyces cerevisiae was cloned and sequenced. The gene was isolated as a multicopy suppressor of a disruption of the SUV-3 gene coding for a DEAD\\/H box protein involved in processing and turnover of mitochondrial transcripts. The DSS-1 gene codes for a 970 amino-acid protein of molecular weight 111 kDa and is necessary for

Aleksandra Dmochowska; Pawel Golik; Piotr P. Stepien

1995-01-01

145

Biogenesis of the preprotein translocase of the outer mitochondrial membrane: protein kinase A phosphorylates the precursor of Tom40 and impairs its import  

PubMed Central

The preprotein translocase of the outer mitochondrial membrane (TOM) functions as the main entry gate for the import of nuclear-encoded proteins into mitochondria. The major subunits of the TOM complex are the three receptors Tom20, Tom22, and Tom70 and the central channel-forming protein Tom40. Cytosolic kinases have been shown to regulate the biogenesis and activity of the Tom receptors. Casein kinase 2 stimulates the biogenesis of Tom22 and Tom20, whereas protein kinase A (PKA) impairs the receptor function of Tom70. Here we report that PKA exerts an inhibitory effect on the biogenesis of the ?-barrel protein Tom40. Tom40 is synthesized as precursor on cytosolic ribosomes and subsequently imported into mitochondria. We show that PKA phosphorylates the precursor of Tom40. The phosphorylated Tom40 precursor is impaired in import into mitochondria, whereas the nonphosphorylated precursor is efficiently imported. We conclude that PKA plays a dual role in the regulation of the TOM complex. Phosphorylation by PKA not only impairs the receptor activity of Tom70, but it also inhibits the biogenesis of the channel protein Tom40. PMID:22419819

Rao, Sanjana; Schmidt, Oliver; Harbauer, Angelika B.; Schönfisch, Birgit; Guiard, Bernard; Pfanner, Nikolaus; Meisinger, Chris

2012-01-01

146

Prohibitin overexpression in adipocytes induces mitochondrial biogenesis, leads to obesity development, and affects glucose homeostasis in a sex-specific manner.  

PubMed

Adipocytes are the primary cells in the body that store excess energy as triglycerides. To perform this specialized function, adipocytes rely on their mitochondria; however, the role of adipocyte mitochondria in the regulation of adipose tissue homeostasis and its impact on metabolic regulation is not understood. We developed a transgenic mouse model, Mito-Ob, overexpressing prohibitin (PHB) in adipocytes. Mito-Ob mice developed obesity due to upregulation of mitochondrial biogenesis in adipocytes. Of note, Mito-Ob female mice developed more visceral fat than male mice. However, female mice exhibited no change in glucose homeostasis and had normal insulin and high adiponectin levels, whereas male mice had impaired glucose homeostasis, compromised brown adipose tissue structure, and high insulin and low adiponectin levels. Mechanistically, we found that PHB overexpression enhances the cross talk between the mitochondria and the nucleus and facilitates mitochondrial biogenesis. The data suggest a critical role of PHB and adipocyte mitochondria in adipose tissue homeostasis and reveal sex differences in the effect of PHB-induced adipocyte mitochondrial remodeling on whole-body metabolism. Targeting adipocyte mitochondria may provide new therapeutic opportunities for the treatment of obesity, a major risk factor for type 2 diabetes. PMID:24947361

Ande, Sudharsana R; Nguyen, K Hoa; Padilla-Meier, G Pauline; Wahida, Wahida; Nyomba, B L Grégoire; Mishra, Suresh

2014-11-01

147

Overexpression of human selenoprotein H in neuronal cells enhances mitochondrial biogenesis and function through activation of protein kinase A, protein kinase B, and cyclic adenosine monophosphate response element-binding protein pathway.  

PubMed

Mitochondrial biogenesis is activated by nuclear encoded transcription co-activator peroxisome proliferator-activated receptor ? coactivator-1? (PGC-1?), which is regulated by several upstream factors including protein kinase A and Akt/protein kinase B. We have previously shown that selenoprotein H enhances the levels of nuclear regulators for mitochondrial biogenesis, increases mitochondrial mass and improves mitochondrial respiratory rate, under physiological condition. Furthermore, overexpression of selenoprotein H protects neuronal HT22 cells from ultraviolet B irradiation-induced cell damage by lowering reactive oxygen species production, and inhibiting activation of caspase-3 and -9, as well as p53. The objective of this study is to identify the cell signaling pathways by which selenoprotein H initiates mitochondrial biogenesis. We first confirmed our previous observation that selenoprotein H transfected HT22 cells increased the protein levels of nuclear-encoded mitochondrial biogenesis factors, peroxisome proliferator-activated receptor ? coactivator-1?, nuclear respiratory factor 1 and mitochondrial transcription factor A. We then observed that total and phosphorylation of protein kinase A, Akt/protein kinase B and cyclic adenosine monophosphate response element-binding protein (CREB) were significantly increased in selenoprotein H transfected cells compared to vector transfected HT22 cells. To verify whether the observed stimulating effects on mitochondrial biogenesis pathways are caused by selenoprotein H and mediated through CREB, we knocked down selenoprotein H mRNA level using siRNA and inhibited CREB with napthol AS-E phosphate in selenoprotein H transfected cells and repeated the measurements of the aforementioned biomarkers. Our results revealed that silencing of selenoprotein H not only decreased the protein levels of PGC-1?, nuclear respiratory factor 1 and mitochondrial transcription factor A, but also decreased the total and phosphorylation levels of protein kinase A, protein kinase B, and CREB. Similarly, CREB inhibition reduced CREB activation and PGC-1? protein levels in selenoprotein H transfected cells. Moreover, selenoprotein H transfection increased the activity of mitochondrial complexes and prevented the ultraviolet B induced fall of mitochondrial membrane potential. We conclude that the effects of selenoprotein H on mitochondrial biogenesis and mitochondrial function are probably mediated through protein kinase A-CREB-PGC-1? and Akt/protein kinase B-CREB-PGC-1? pathways. PMID:23220172

Mehta, Suresh L; Mendelev, Natalia; Kumari, Santosh; Andy Li, P

2013-03-01

148

Overexpression of human selenoprotein H in neuronal cells enhances mitochondrial biogenesis and function through activation of protein kinase A, protein kinase B, and cyclic adenosine monophosphate response element-binding protein pathway  

PubMed Central

Mitochondrial biogenesis is activated by nuclear encoded transcription co-activator peroxisome proliferator–activated receptor ? coactivator-1? (PGC-1?), which is regulated by several upstream factors including protein kinase A and Akt/protein kinase B. We have previously shown that selenoprotein H enhances the levels of nuclear regulators for mitochondrial biogenesis, increases mitochondrial mass and improves mitochondrial respiratory rate, under physiological condition. Furthermore, overexpression of selenoprotein H protects neuronal HT22 cells from ultraviolet B irradiation-induced cell damage by lowering reactive oxygen species production, and inhibiting activation of caspase-3 and -9, as well as p53. The objective of this study is to identify the cell signaling pathways by which selenoprotein H initiates mitochondrial biogenesis. We first confirmed our previous observation that selenoprotein H transfected HT22 cells increased the protein levels of nuclear-encoded mitochondrial biogenesis factors, peroxisome proliferator–activated receptor ? coactivator-1?, nuclear respiratory factor 1 and mitochondrial.transcription factor A, We then observed that total and phosphorylation of protein kinase A, Akt/protein kinase B and cyclic adenosine monophosphate response element-binding protein (CREB) were significantly increased in selenoprotein H transfected cells compared to vector transfected HT22 cells. To verify whether the observed stimulating effects on mitochondrial biogenesis pathways are caused by selenoprotein H and mediated through CREB, we knocked down selenoprotein H mRNA level using siRNA and inhibited CREB with napthol AS-E phosphate in selenoprotein H transfected cells and repeated the measurements of the aforementioned biomarkers. Our results revealed that silencing of selenoprotein H not only decreased the protein levels of PGC-1?, nuclear respiratory factor 1 and mitochondrial transcription factor A, but also decreased the total and phosphorylation levels of protein kinase A, protein kinase B, and CREB. Similarly, CREB inhibition reduced CREB activation and PGC-1? protein levels in selenoprotein H transfected cells. Moreover, selenoprotein H transfection increased the activity of mitochondrial complexes and prevented the ultraviolet B induced fall of mitochondrial membrane potential. We conclude that the effects of selenoprotein H on mitochondrial biogenesis and mitochondrial function are probably mediated through protein kinase A- CREB- PGC-1? and Akt/proetin kinase B- CREB- PGC-1? pathways. PMID:23220172

Mehta, Suresh L.; Mendelev, Natalia; Kumari, Santosh; Li, P. Andy

2013-01-01

149

Exercise-induced leukocyte apoptosis.  

PubMed

Physical exercise is well known to affect leukocyte numbers and function. While regular exercise training has been shown to enhance specific immune functions, acute bouts of intensive exercise often lead to a pro-inflammatory response accompanied by a transient lymphocytopenia and neutrophilia. It can be assumed, that lymphocytopenia can be attributed at least partially to an enhanced lymphocyte apoptosis. In contrast, regulation of neutrophil apoptosis after exercise remains controversial since studies demonstrated both an up-regulation as well as a down-regulation of cell death. However, these discrepancies may be due to differences in exercise protocols, subjects' fitness levels, and to different methodological approaches. Two major signalling pathways of exercise induced apoptosis have been identified. First the external receptor mediated pathway using death receptors, and second the internal, oxidative-mediated pathway which encompasses the mitochondria. Potential apoptosis modulating mediators are reactive oxygen species (ROS), glucocorticoids and cytokines which are part of the systemic inflammatory response evoked after acute intensive exercise. Finally, the physiological impact and clinical relevance of leukocyte apoptosis will be discussed. On the one hand, exercise-induced apoptosis might be a mechanism to remove activated and potentially autoreactive immune cells. On the other hand, apoptosis might be a regulatory mechanism which is necessary for tissue reorganization and adaptational training processes. PMID:24974724

Krüger, Karsten; Mooren, Frank C

2014-01-01

150

Dietary Fucoxanthin Increases Metabolic Rate and Upregulated mRNA Expressions of the PGC-1alpha Network, Mitochondrial Biogenesis and Fusion Genes in White Adipose Tissues of Mice  

PubMed Central

The mechanism for how fucoxanthin (FX) suppressed adipose accumulation is unclear. We aim to investigate the effects of FX on metabolic rate and expressions of genes related to thermogenesis, mitochondria biogenesis and homeostasis. Using a 2 × 2 factorial design, four groups of mice were respectively fed a high sucrose (50% sucrose) or a high-fat diet (23% butter + 7% soybean oil) supplemented with or without 0.2% FX. FX significantly increased oxygen consumption and carbon dioxide production and reduced white adipose tissue (WAT) mass. The mRNA expressions of peroxisome proliferator-activated receptor (PPAR) ? coactivator-1? (PGC-1?), cell death-inducing DFFA-like effecter a (CIDEA), PPAR?, PPAR?, estrogen-related receptor ? (ERR?), ?3-adrenergic receptor (?3-AR) and deiodinase 2 (Dio2) were significantly upregulated in inguinal WAT (iWAT) and epididymal WAT (eWAT) by FX. Mitochondrial biogenic genes, nuclear respiratory factor 1 (NRF1) and NRF2, were increased in eWAT by FX. Noticeably, FX upregulated genes of mitochondrial fusion, mitofusin 1 (Mfn1), Mfn2 and optic atrophy 1 (OPA1), but not mitochondrial fission, Fission 1, in both iWAT and eWAT. In conclusion, dietary FX enhanced the metabolic rate and lowered adipose mass irrespective of the diet. These were associated with upregulated genes of the PGC-1? network and mitochondrial fusion in eWAT and iWAT. PMID:24534841

Wu, Meng-Ting; Chou, Hong-Nong; Huang, Ching-jang

2014-01-01

151

Sex-dependent differences in rat brown adipose tissue mitochondrial biogenesis and insulin signaling parameters in response to an obesogenic diet.  

PubMed

Marked sex-dependent differences in mitochondrial function and redox status have been found in brown adipose tissue (BAT) of control rats. Insulin also plays a role in the development and maintenance of this tissue. The aim was to investigate sexual dimorphism in the effects of diet-induced obesity on BAT mitochondrial function, as well as on insulin signaling pathway. 10-week-old Wistar rats of both sexes were fed a control diet or a palatable high-fat diet for 26 weeks. Serum markers of insulin sensitivity were analyzed. Mitochondrial DNA (mtDNA) content, mitochondrial oxidative activities, PGC-1? mRNA levels, as well as the protein levels of insulin receptor subunit ? (IR?), glucose transporter GLUT4, ?(3)-adrenergic receptor (?(3)-AR), phosphatidylinositol 3-kinase, mitochondrial transcription factor A (TFAM), cytochrome c oxidase subunit IV (COX IV), and uncoupling protein 1 (UCP1) were measured in BAT. Obese females showed impaired systemic insulin sensitivity accompanied by diminished IR?, GLUT4, and ?(3)-AR protein levels in BAT. In addition, TFAM and COX IV protein and PGC-1? mRNA levels decreased in obese females, whereas mtDNA levels increased. In obese males, oxidative and thermogenic capacities rose and no significant changes were observed in the insulin signaling pathway elements. The reduction of the insulin signaling pathway in BAT of obese females may be responsible, at least partially, for the impaired biogenesis process, which could favor the increase of body weight found in this sex. In contrast, the enhanced mitochondrial functionality in the BAT of males would avoid increased oxidative damage and the impairment of insulin signaling. PMID:23108789

Nadal-Casellas, A; Bauzá-Thorbrügge, M; Proenza, A M; Gianotti, M; Lladó, I

2013-01-01

152

PPR2263, a DYW-Subgroup Pentatricopeptide Repeat Protein, Is Required for Mitochondrial nad5 and cob Transcript Editing, Mitochondrion Biogenesis, and Maize Growth[C][W  

PubMed Central

RNA editing plays an important role in organelle gene expression in various organisms, including flowering plants, changing the nucleotide information at precise sites. Here, we present evidence that the maize (Zea mays) nuclear gene Pentatricopeptide repeat 2263 (PPR2263) encoding a DYW domain–containing PPR protein is required for RNA editing in the mitochondrial NADH dehydrogenase5 (nad5) and cytochrome b (cob) transcripts at the nad5-1550 and cob-908 sites, respectively. Its putative ortholog, MITOCHONDRIAL EDITING FACTOR29, fulfills the same role in Arabidopsis thaliana. Both the maize and the Arabidopsis proteins show preferential localization to mitochondria but are also detected in chloroplasts. In maize, the corresponding ppr2263 mutation causes growth defects in kernels and seedlings. Embryo and endosperm growth are reduced, leading to the production of small but viable kernels. Mutant plants have narrower and shorter leaves, exhibit a strong delay in flowering time, and generally do not reach sexual maturity. Whereas mutant chloroplasts do not have major defects, mutant mitochondria lack complex III and are characterized by a compromised ultrastructure, increased transcript levels, and the induction of alternative oxidase. The results suggest that mitochondrial RNA editing at the cob-908 site is necessary for mitochondrion biogenesis, cell division, and plant growth in maize. PMID:22319053

Sosso, Davide; Mbelo, Sylvie; Vernoud, Vanessa; Gendrot, Ghislaine; Dedieu, Annick; Chambrier, Pierre; Dauzat, Myriam; Heurtevin, Laure; Guyon, Virginie; Takenaka, Mizuki; Rogowsky, Peter M.

2012-01-01

153

Exercise-induced Pulmonary Hypertension  

PubMed Central

Exercise stresses the pulmonary circulation through increases in cardiac output (Q.) and left atrial pressure. Invasive as well as noninvasive studies in healthy volunteers show that the slope of mean pulmonary artery pressure (mPAP)–flow relationships ranges from 0.5 to 3 mm Hg?min?L?1. The upper limit of normal mPAP at exercise thus approximates 30 mm Hg at a Q. of less than 10 L?min?1 or a total pulmonary vascular resistance at exercise of less than 3 Wood units. Left atrial pressure increases at exercise with an average upstream transmission to PAP in a close to one-for-one mm Hg fashion. Multipoint PAP–flow relationships are usually described by a linear approximation, but present with a slight curvilinearity, which is explained by resistive vessel distensibility. When mPAP is expressed as a function of oxygen uptake or workload, plateau patterns may be observed in patients with systolic heart failure who cannot further increase Q. at the highest levels of exercise. Exercise has to be dynamic to avoid the increase in systemic vascular resistance and abrupt changes in intrathoracic pressure that occur with resistive exercise and can lead to unpredictable effects on the pulmonary circulation. Postexercise measurements are unreliable because of the rapid return of pulmonary vascular pressures and flows to the baseline resting state. Recent studies suggest that exercise-induced increase in PAP to a mean higher than 30 mm Hg may be associated with dyspnea-fatigue symptomatology. PMID:23348976

Vanderpool, Rebecca; Dhakal, Bishnu P.; Saggar, Rajeev; Saggar, Rajan; Vachiery, Jean-Luc; Lewis, Gregory D.

2013-01-01

154

Dynamic changes in mitochondrial biogenesis and antioxidant enzymes during the spontaneous differentiation of human embryonic stem cells  

Microsoft Academic Search

Embryonic cells before implantation are exposed to a hypoxic condition and dependent on anaerobic metabolism. Human embryonic stem cells (HESCs) derived from pre-implantation blastocyst also grow well in hypoxic conditions. Expecting that the differentiating HESCs might mimic anaerobic-to-aerobic metabolic transition of the early human life, we examined the mitochondria-related changes in these cells. We observed that mitochondrial mass and mitochondrial

Young Min Cho; Sujin Kwon; Youngmi Kim Pak; Hye Won Seol; Young Min Choi; Do Joon Park; Kyong Soo Park; Hong Kyu Lee

2006-01-01

155

The Role of Heme and Iron-Sulfur Clusters in Mitochondrial Biogenesis, Maintenance, and Decay with Age  

Microsoft Academic Search

Mitochondria decay with age from oxidative damage and loss of protective mechanisms. Resistance, repair, and replacement mechanisms are essential for mitochondrial preservation and maintenance. Iron plays an essential role in the maintenance of mitochondria, through its two major functional forms: heme and iron-sulfur clusters. Both iron-based cofactors are formed and utilized in the mitochondria and then distributed throughout the cell.

Hani Atamna; Patrick B Walter; Bruce N Ames

2002-01-01

156

Chitooligosaccharide Induces Mitochondrial Biogenesis and Increases Exercise Endurance through the Activation of Sirt1 and AMPK in Rats  

Microsoft Academic Search

By catabolizing glucose and lipids, mitochondria produce ATPs to meet energy demands. When the number and activity of mitochondria are not sufficient, the human body becomes easily fatigued due to the lack of ATP, thus the control of the quantity and function of mitochondria is important to optimize energy balance. By increasing mitochondrial capacity? it may be possible to enhance

Hyun Woo Jeong; Si Young Cho; Shinae Kim; Eui Seok Shin; Jae Man Kim; Min Jeong Song; Pil Joon Park; Jong Hee Sohn; Hyon Park; Dae-Bang Seo; Wan Gi Kim; Sang-Jun Lee

2012-01-01

157

J Physiol 577.2 (2006) pp 739751 739 Temperature-and exercise-induced gene expression  

E-print Network

remodelling and mitochondrial biogenesis are thought to occur through a series of cellular events that begin) were either swim trained or cold acclimatized for 4 weeks. We found that the mitochondrial marker in mitochondrial mass and the upregulation of metabolic pathwaysinvolvedinaerobicmetabolism

McClelland, Grant B.

158

Acetyl-L-carnitine activates the peroxisome proliferator-activated receptor-? coactivators PGC-1?/PGC-1?-dependent signaling cascade of mitochondrial biogenesis and decreases the oxidized peroxiredoxins content in old rat liver.  

PubMed

The behavior of the peroxisome proliferator-activated receptor-? coactivators PGC-1?/PGC-?-dependent mitochondrial biogenesis signaling pathway, as well as the level of some antioxidant enzymes and proteins involved in mitochondrial dynamics in the liver of old rats before and after 2 months of acetyl-L-carnitine (ALCAR) supplementation, was tested. The results reveal that ALCAR treatment is able to reverse the age-associated decline of PGC-1?, PGC-1?, nuclear respiratory factor 1 (NRF-1), mitochondrial transcription factor A (TFAM), nicotinamide adenine dinucleotide (NADH) dehydrogenase subunit 1 (ND1), and cytochrome c oxidase subunit IV (COX IV) protein levels, of mitochondrial DNA (mtDNA) content, and of citrate synthase activity. Moreover, it partially reverses the mitochondrial superoxide dismutase 2 (SOD2) decline and reduces the cellular content of oxidized peroxiredoxins. These data demonstrate that ALCAR treatment is able to promote in the old rat liver a new mitochondrial population that can contribute to the cellular oxidative stress reduction. Furthermore, a remarkable decline of Drp1 and of Mfn2 proteins is reported here for the first time, suggesting a reduced mitochondrial dynamics in aging liver with no effect of ALCAR treatment. PMID:22533417

Pesce, Vito; Nicassio, Luigi; Fracasso, Flavio; Musicco, Clara; Cantatore, Palmiro; Gadaleta, Maria Nicola

2012-04-01

159

Carbohydrate restricted recovery from long term endurance exercise does not affect gene responses involved in mitochondrial biogenesis in highly trained athletes.  

PubMed

The aim was to determine if the metabolic adaptations, particularly PGC-1? and downstream metabolic genes were affected by restricting CHO following an endurance exercise bout in trained endurance athletes. A second aim was to compare baseline expression level of these genes to untrained. Elite endurance athletes (VO2max 66 ± 2 mL·kg(-1)·min(-1), n = 15) completed 4 h cycling at ~56% VO2max. During the first 4 h recovery subjects were provided with either CHO or only H2O and thereafter both groups received CHO. Muscle biopsies were collected before, after, and 4 and 24 h after exercise. Also, resting biopsies were collected from untrained subjects (n = 8). Exercise decreased glycogen by 67.7 ± 4.0% (from 699 ± 26.1 to 239 ± 29.5 mmol·kg(-1)·dw(-1)) with no difference between groups. Whereas 4 h of recovery with CHO partly replenished glycogen, the H2O group remained at post exercise level; nevertheless, the gene expression was not different between groups. Glycogen and most gene expression levels returned to baseline by 24 h in both CHO and H2O. Baseline mRNA expression of NRF-1, COX-IV, GLUT4 and PPAR-? gene targets were higher in trained compared to untrained. Additionally, the proportion of type I muscle fibers positively correlated with baseline mRNA for PGC-1?, TFAM, NRF-1, COX-IV, PPAR-?, and GLUT4 for both trained and untrained. CHO restriction during recovery from glycogen depleting exercise does not improve the mRNA response of markers of mitochondrial biogenesis. Further, baseline gene expression of key metabolic pathways is higher in trained than untrained. PMID:25677542

Jensen, Line; Gejl, Kasper D; Ørtenblad, Niels; Nielsen, Jakob L; Bech, Rune D; Nygaard, Tobias; Sahlin, Kent; Frandsen, Ulrik

2015-02-01

160

Exercise-Induced Anaphylaxis and Food-Dependent Exercise-Induced Anaphylaxis  

Microsoft Academic Search

\\u000a Exercise-induced anaphylaxis (EIAn) is characterized by symptoms of anaphylaxis in the setting of significant physical exertion.\\u000a A food-dependent form of exercise-induced ­anaphylaxis also exists, in which symptoms develop only if the patient has eaten\\u000a in the hours immediately preceding exercise. In most patients with the food-dependent form, only a specific food(s) will elicit\\u000a symptoms when combined with exercise, and patients

Anna M. Feldweg; Albert L. Sheffer

161

Exercise-induced anaphylaxis: A clinical view  

PubMed Central

Exercise-induced anaphylaxis (EIA) is a distinct form of physical allergy. The development of anaphylaxis during exertion often requires the concomitant exposure to triggering factors such as intake of foods (food dependent exercise-induced anaphylaxis) or drugs prior to exercise, extreme environmental conditions. EIA is a rare, but serious disorder, which is often undetected or inadequately treated. This article summarizes current evidences on pathophysiology, diagnosis and management. We reviewed recent advances in factors triggering the release of mediators from mast cells which seems to play a pathogenetic role. A correct diagnosis is essential to avoid unnecessary restricted diet, to allow physical activity in subjects with EIA dependent from triggering factors such as food, and to manage attacks. An algorithm for diagnosing EIA based on medical history, IgE tests and exercise challenge test has been provided. In the long-term management of EIA, there is a need for educating patients and care-givers to avoid exposure to precipitating factors and to recognize and treat episodes. Future researches on existing questions are discussed. PMID:22980517

2012-01-01

162

Peroxisome Proliferator-activated Receptor ? Co-activator 1-? as a Critical Co-activator of the Murine Hepatic Oxidative Stress Response and Mitochondrial Biogenesis in Staphylococcus aureus Sepsis*  

PubMed Central

A key transcriptional regulator of cell metabolism, the peroxisome proliferator-activated receptor ? co-activator 1-? (PPARGC-1-? or PGC-1?), also regulates mitochondrial biogenesis, but its role in antioxidant gene regulation is not well understood. Here, we asked whether genetic heterozygosity of PGC-1? modulates gene expression for the mitochondrial antioxidant enzyme SOD-2 during hepatic inflammatory stress. Using Staphylococcus aureus peritonitis in mice, we found significant Sod2 gene induction in WT mice, whereas PGC-1? heterozygotes (PGC-1?+/?) failed to augment Sod2 mRNA and protein levels. Impaired Sod2 regulation in PGC-1?+/? mice was accompanied by oxidative stress shown by elevated mitochondrial GSSG/GSH and protein carbonyls. In silico analysis of the mouse proximal Sod2 promoter region revealed consensus binding sites for the Nfe2l2 (Nrf2) transcription factor. Chromatin immunoprecipitation demonstrated diminished Nfe2l2 protein binding to the antioxidant response element promoter site proximal to the Sod2 start site in PGC-1? heterozygous mice, implicating PGC-1? in facilitation of Nfe2l2 DNA binding. Nuclear protein co-immunoprecipitation demonstrated an interaction between hepatic Nfe2l2 and PGC-1? in WT mice that was greatly reduced in PGC-1?+/? mice. The data indicate that PGC-1? promotes mitochondrial antioxidant enzyme expression through Nfe2l2-mediated SOD-2 expression in sepsis. The presence of this new PGC-1?-dependent signaling axis indicates that PGC-1? opposes mitochondrial oxidative stress by means of selective induction of one or more antioxidant response element-driven genes. By implication, exploitation of this axis could lead to new pharmacological interventions to improve the antioxidant defenses during oxidative stress-induced mitochondrial damage. PMID:24253037

Cherry, Anne D.; Suliman, Hagir B.; Bartz, Raquel R.; Piantadosi, Claude A.

2014-01-01

163

Auxin Biogenesis  

PubMed Central

Subcellular fractionation of cucumber (Cucumis sativus L.) seedlings was achieved, and two of the enzymes in the auxin biosynthetic pathway were localized. NADH-specific indoleacetaldehyde reductase activity was observed only in the cytosol fractions obtained from separated hypocotyl and cotyledon tissue. In contrast, a portion of the NADPH-specific indoleacetaldehyde reductase activity was associated with a microsomal fraction derived from these tissues. The NADPH-specific indoleacetaldehyde reductase was consistently found to be more firmly associated with the microsomal fraction derived from hypocotyls than with that from the cotyledons. These results indicate a division of the terminal steps of auxin biogenesis into at least two subcellular compartments. PMID:16659584

Bower, Peter J.; Brown, Hugh M.; Purves, William K.

1976-01-01

164

Thyromimetic Action of the Peroxisome Proliferators Clofibrate, Perfluorooctanoic Acid, and Acetylsalicylic Acid Includes Changes in mRNA Levels for Certain Genes Involved in Mitochondrial Biogenesis  

Microsoft Academic Search

The effects of three peroxisome proliferators on the mRNA levels for some mitochondrial inner-membrane proteins in rat liver were investigated. Clofibrate, perfluorooctanoic acid, and acetylsalicylic acid all increased the mRNA levels for the mitochondrial-encoded respiratory-chain components cytochromecoxidase subunit I and NADH dehydrogenase subunit I. Mitochondrial 16S rRNA was also induced by clofibrate. The mRNA levels for the nuclear-encoded mitochondrial inner-membrane

Yanong Cai; B. Dean Nelson; Ronggui Li; Katarina Luciakova; Joseph W. DePierre

1996-01-01

165

Mitochondrial adaptations evoked with exercise are associated with a reduction in age-induced testicular atrophy in Fischer-344 rats.  

PubMed

Mitochondrial dysfunction in various tissues has been associated with numerous conditions including aging. In testes, aging induces atrophy and a decline in male reproductive function but the involvement of mitochondria is not clear. The purpose of this study was to examine whether the mitochondrial profile differed with (1) aging, and (2) 10-weeks of treadmill exercise training, in the testes of young (6 month) and old (24 month) Fischer-344 (F344) animals. Old animals exhibited significant atrophy (30 % decline; P < 0.05) in testes compared to young animals. However, relative mitochondrial content was not reduced with age and this was consistent with the lack of change in the mitochondrial biogenesis regulator protein, peroxisome proliferator-activated receptor gamma coactivator 1-alpha and its downstream targets nuclear respiratory factor-1 and mitochondrial transcription factor A. No effect was observed in the pro- or anti-apoptotic proteins, Bax and Bcl-2, respectively, but age increased apoptosis inducing factor levels. Endurance training induced beneficial mitochondrial adaptations that were more prominent in old animals including greater increases in relative mtDNA content, biogenesis/remodeling (mitofusin 2), antioxidant capacity (mitochondrial superoxide dismutase) and lower levels of phosphorylated histone H2AX, an early marker of DNA damage (P < 0.05). Importantly, these exercise-induced changes were associated with an attenuation of testes atrophy in older sedentary animals (P < 0.05). Our results indicate that aging-induced atrophy in testes may not be associated with changes in relative mitochondrial content and key regulatory proteins and that exercise started in late-life elicits beneficial changes in mitochondria that may protect against age-induced testicular atrophy. PMID:25108553

Joseph, A-M; Nguyen, L M-D; Welter, A E; Dominguez, J M; Behnke, B J; Adhihetty, P J

2014-10-01

166

Fatal buckwheat dependent exercised-induced anaphylaxis.  

PubMed

Cases of food-dependent exercise-induced anaphylaxis (FEA) caused by buckwheat have been rare. Clinical, laboratory, and autopsy findings are present on an 8-year old girl with FEA caused by Japanese buckwheat. The patient consumed buckwheat noodles called "zaru soba" and immediately thereafter swam vigorously. Approximately 30 minutes later, she complained of abdominal pain, vomiting, coughing, and chest discomfort. Another ten minutes later her consciousness level deteriorated and she experienced cardiorespiratory arrest. The heart beat was restored and she was admitted to the hospital. She never regained consciousness and expired after another arrest 13 days later. Her IgE level was high (2,840 IU/ml) and the IgE-radioallergosorbent test (RAST) score was 2 for soybeans, 3 for buckwheat, 2 for rice, and 3 for wheat. An exaggerated hematemesis that occurred immediately after hospital admission indicated an inflammatory condition of the digestive tract that was caused by buckwheat. Marked ulceration accompanied with hemorrhage and necrosis was noted at the ileum. Extensive hemorrhage involving the endotracheal pulmonary field and lymphocyte infiltration of the alveolar space likely appeared after the inflammation. The analysis of buckwheat-specific IgE antibody by immunoblotting showed 7 bands that reacted with the IgE of the patient's serum, 4 bands: 16, 20, 24, and 58 kDa, were specific to the patient as compared to subjects not allergic to buckwheat. A first case of fatal FEA by buckwheat is reported with reference to specific IgE. PMID:12009078

Noma, T; Yoshizawa, I; Ogawa, N; Ito, M; Aoki, K; Kawano, Y

2001-12-01

167

Suppression of mitochondrial biogenesis through toll-like receptor 4-dependent mitogen-activated protein kinase kinase/extracellular signal-regulated kinase signaling in endotoxin-induced acute kidney injury.  

PubMed

Although disruption of mitochondrial homeostasis and biogenesis (MB) is a widely accepted pathophysiologic feature of sepsis-induced acute kidney injury (AKI), the molecular mechanisms responsible for this phenomenon are unknown. In this study, we examined the signaling pathways responsible for the suppression of MB in a mouse model of lipopolysaccharide (LPS)-induced AKI. Downregulation of peroxisome proliferator-activated receptor ? coactivator-1? (PGC-1?), a master regulator of MB, was noted at the mRNA level at 3 hours and protein level at 18 hours in the renal cortex, and was associated with loss of renal function after LPS treatment. LPS-mediated suppression of PGC-1? led to reduced expression of downstream regulators of MB and electron transport chain proteins along with a reduction in renal cortical mitochondrial DNA content. Mechanistically, Toll-like receptor 4 (TLR4) knockout mice were protected from renal injury and disruption of MB after LPS exposure. Immunoblot analysis revealed activation of tumor progression locus 2/mitogen-activated protein kinase kinase/extracellular signal-regulated kinase (TPL-2/MEK/ERK) signaling in the renal cortex by LPS. Pharmacologic inhibition of MEK/ERK signaling attenuated renal dysfunction and loss of PGC-1?, and was associated with a reduction in proinflammatory cytokine (e.g., tumor necrosis factor-? [TNF-?], interleukin-1?) expression at 3 hours after LPS exposure. Neutralization of TNF-? also blocked PGC-1? suppression, but not renal dysfunction, after LPS-induced AKI. Finally, systemic administration of recombinant tumor necrosis factor-? alone was sufficient to produce AKI and disrupt mitochondrial homeostasis. These findings indicate an important role for the TLR4/MEK/ERK pathway in both LPS-induced renal dysfunction and suppression of MB. TLR4/MEK/ERK/TNF-? signaling may represent a novel therapeutic target to prevent mitochondrial dysfunction and AKI produced by sepsis. PMID:25503387

Smith, Joshua A; Stallons, L Jay; Collier, Justin B; Chavin, Kenneth D; Schnellmann, Rick G

2015-02-01

168

Investigation of an Exercise-Induced State of Hypofrontality.  

E-print Network

?? The reticular-activating hypofrontality model of acute exercise (RAH) predicts exercise-induced hypoactivity in frontal cortex which mediates executive function. Connors Continuous Performance Test (CCPT) was… (more)

Wohlwend, Martin

2012-01-01

169

Wheezing or Breezing through Exercise-Induced Asthma.  

ERIC Educational Resources Information Center

Several physicians discuss the tests they use to diagnose exercise-induced asthma (EIA), the medications they typically prescribe and why, and the importance of properly educating athletes about EIA. (JD)

McCarthy, Paul

1989-01-01

170

Defects of mtDNA Replication Impaired Mitochondrial Biogenesis During Trypanosoma cruzi Infection in Human Cardiomyocytes and Chagasic Patients: The Role of Nrf1/2 and Antioxidant Response  

PubMed Central

Background Mitochondrial dysfunction is a key determinant in chagasic cardiomyopathy development in mice; however, its relevance in human Chagas disease is not known. We determined if defects in mitochondrial biogenesis and dysregulation of peroxisome proliferator-activated receptor gamma (PPAR?) coactivator-1 (PGC-1)–regulated transcriptional pathways constitute a mechanism or mechanisms underlying mitochondrial oxidative-phosphorylation (OXPHOS) deficiency in human Chagas disease. Methods and Results We utilized human cardiomyocytes and left-ventricular tissue from chagasic and other cardiomyopathy patients and healthy donors (n>6/group). We noted no change in citrate synthase activity, yet mRNA and/or protein levels of subunits of the respiratory complexes were significantly decreased in Trypanosoma cruzi–infected cardiomyocytes (0 to 24 hours) and chagasic hearts. We observed increased mRNA and decreased nuclear localization of PGC-1-coactivated transcription factors, yet the expression of genes for PPAR?-regulated fatty acid oxidation and nuclear respiratory factor (NRF1/2)–regulated mtDNA replication and transcription machinery was enhanced in infected cardiomyocytes and chagasic hearts. The D-loop formation was normal or higher, but mtDNA replication and mtDNA content were decreased by 83% and 40% to 65%, respectively. Subsequently, we noted that reactive oxygen species (ROS), oxidative stress, and mtDNA oxidation were significantly increased, yet NRF1/2-regulated antioxidant gene expression remained compromised in infected cardiomyocytes and chagasic hearts. Conclusions The replication of mtDNA was severely compromised, resulting in a significant loss of mtDNA and expression of OXPHOS genes in T cruzi–infected cardiomyocytes and chagasic hearts. Our data suggest increased ROS generation and selective functional incapacity of NRF2-mediated antioxidant gene expression played a role in the defects in mtDNA replication and unfitness of mtDNA for replication and gene expression in Chagas disease. PMID:23316324

Wan, Xianxiu; Gupta, Shivali; Zago, Maria P.; Davidson, Mercy M.; Dousset, Pierre; Amoroso, Alejandro; Garg, Nisha Jain

2012-01-01

171

Role of Magmas in protein transport and human mitochondria biogenesis  

E-print Network

Role of Magmas in protein transport and human mitochondria biogenesis Devanjan Sinha, Neha Joshi mitochondrial inner membrane. Human Magmas shows a complete growth complementation of Dpam16 yeast cells at all and is peripherally associated with inner mitochondrial membrane in yeast and humans. Magmas forms a stable subcomplex

D' Silva, Patrick

172

Exercise- and training-induced upregulation of skeletal muscle fatty acid oxidation are not solely dependent on mitochondrial machinery and biogenesis.  

PubMed

? Regulation of skeletal muscle fatty acid oxidation (FAO) and adaptation to exercise training have long been thought to depend on delivery of fatty acids (FAs) to muscle, their diffusion into muscle, and muscle mitochondrial content and biochemical machinery. However, FA entry into muscle occurs via a regulatable, protein-mediated mechanism, involving several transport proteins. Among these CD36 is key. Muscle contraction and pharmacological agents induce CD36 to translocate to the cell surface, a response that regulates FA transport, and hence FAO. In exercising CD36 KO mice, exercise duration (-44%), and FA transport (-41%) and oxidation (-37%) are comparably impaired, while carbohydrate metabolism is augmented. In trained CD36 KO mice, training-induced upregulation of FAO is not observed, despite normal training-induced increases in mitochondrial density and enzymes. Transfecting CD36 into sedentary WT muscle (+41%), comparable to training-induced CD36 increases (+44%) in WT muscle, markedly upregulates FAO to rates observed in trained WT mice, but without any changes in mitochondrial density and enzymes. Evidently, in vivo CD36-mediated FA transport is key for muscle fuel selection and training-induced FAO upregulation, independent of mitochondrial adaptations. This CD36 molecular mechanism challenges the view that skeletal muscle FAO is solely regulated by muscle mitochondrial content and machinery. PMID:22890711

Yoshida, Yuko; Jain, Swati S; McFarlan, Jay T; Snook, Laelie A; Chabowski, Adrian; Bonen, Arend

2013-09-15

173

Human mitochondrial ferritin improves respiratory function in yeast mutants deficient in iron-sulfur cluster biogenesis, but is not a functional homologue of yeast frataxin.  

PubMed

We overexpressed human mitochondrial ferritin in frataxin-deficient yeast cells (?yfh1), but also in another mutant affected in [Fe-S] assembly (?ggc1). Ferritin was correctly processed and expressed in the mitochondria of these cells, but the fraction of total mitochondrial iron bound to ferritin was very low, and most of the iron remained in the form of insoluble particles of ferric phosphate in these mitochondria, as evidenced by gel filtration analysis of the mitochondrial matrix (fast protein liquid chromatography [FPLC]) and by Mössbauer spectroscopy. Mutant cells in which ferritin was overexpressed still accumulated iron in the mitochondria and remained deficient in [Fe-S] assembly, suggesting that human mitochondrial ferritin is not a functional homologue of yeast frataxin. However, the respiratory function was improved in these mutants, which correlates with an improvement of cytochrome and heme synthesis. Overexpression of mitochondrial ferritin in [Fe-S] mutants resulted in the appearance of a small pool of high-spin ferrous iron in the mitochondria, which was probably responsible for the improvement of heme synthesis and of the respiratory function in these mutants. PMID:22950017

Sutak, Robert; Seguin, Alexandra; Garcia-Serres, Ricardo; Oddou, Jean-Louis; Dancis, Andrew; Tachezy, Jan; Latour, Jean-Marc; Camadro, Jean-Michel; Lesuisse, Emmanuel

2012-06-01

174

Human mitochondrial ferritin improves respiratory function in yeast mutants deficient in iron–sulfur cluster biogenesis, but is not a functional homologue of yeast frataxin  

PubMed Central

We overexpressed human mitochondrial ferritin in frataxin-deficient yeast cells (?yfh1), but also in another mutant affected in [Fe-S] assembly (?ggc1). Ferritin was correctly processed and expressed in the mitochondria of these cells, but the fraction of total mitochondrial iron bound to ferritin was very low, and most of the iron remained in the form of insoluble particles of ferric phosphate in these mitochondria, as evidenced by gel filtration analysis of the mitochondrial matrix (fast protein liquid chromatography [FPLC]) and by Mössbauer spectroscopy. Mutant cells in which ferritin was overexpressed still accumulated iron in the mitochondria and remained deficient in [Fe-S] assembly, suggesting that human mitochondrial ferritin is not a functional homologue of yeast frataxin. However, the respiratory function was improved in these mutants, which correlates with an improvement of cytochrome and heme synthesis. Overexpression of mitochondrial ferritin in [Fe-S] mutants resulted in the appearance of a small pool of high-spin ferrous iron in the mitochondria, which was probably responsible for the improvement of heme synthesis and of the respiratory function in these mutants. PMID:22950017

Sutak, Robert; Seguin, Alexandra; Garcia-Serres, Ricardo; Oddou, Jean-Louis; Dancis, Andrew; Tachezy, Jan; Latour, Jean-Marc; Camadro, Jean-Michel; Lesuisse, Emmanuel

2012-01-01

175

Cysteine desulfurase Nfs1 and Pim1 protease control levels of Isu, the Fe-S cluster biogenesis scaffold  

E-print Network

of the plasma and mitochondrial membranes (3). A single Fe-S cluster biogenesis system closely relatedCysteine desulfurase Nfs1 and Pim1 protease control levels of Isu, the Fe-S cluster biogenesis posttranslationally on disruption of the cluster biogenesis system. Here we report that Isu is degraded by the Lon

Craig, Elizabeth A

176

Exercise-induced asthma. What family physicians should do.  

PubMed Central

Exercise-induced asthma is described as a transitory increase in airway resistance during or after vigorous exercise. Nearly 90% of patients with chronic asthma and 40% of allergic nonasthmatic patients have the condition. Family physicians should try to educate patients about their asthma and, barring contraindications, encourage them to participate in regular physical activity. PMID:8563507

D'Urzo, A.

1995-01-01

177

EXERCISE-INDUCED PULMONARY HEMORRHAGE AFTER RUNNING A MARATHON  

EPA Science Inventory

We report on a healthy 26-year-old male who had an exercise-induced pulmonary hemorrhage (EIPH) within 24 hours of running a marathon. There were no symptoms, abnormalities on exam, or radiographic infiltrates. He routinely participated in bronchoscopy research and the EIPH was e...

178

Coping with Exercise-Induced Asthma in Sports.  

ERIC Educational Resources Information Center

This article reviews the history of research on exercise-induced asthma (EIA) and the pathophysiology of the condition, including its development and influencing factors. Four groups of drugs that are effective against EIA--theopyhlline, beta-adrenergic agents, cromolyn sodium, and anticholinergics--are discussed. (Author/CB)

Katz, Roger M.

1987-01-01

179

Diagnosis and Management of Exercise-Induced Asthma.  

ERIC Educational Resources Information Center

Exercise-induced asthma (EIA) affects 12-15% of the population. This comprehensive guide suggests that nearly all individuals with EIA can be active, highlighting both pharmacologic and nonpharmacologic management of asthma and stressing the importance of rigorous patient education in controlling underlying asthma and EIA. (SM)

Rupp, Ned T.

1996-01-01

180

Systematic identification of human mitochondrial disease genes through integrative genomics  

E-print Network

, coexpression and transcriptional induction during mitochondrial biogenesis. Through an integrated analysis we in gene expression during mitochondrial biogenesis induced by PGC-1a 2,361 68 Maestro 1,451 10 EightSystematic identification of human mitochondrial disease genes through integrative genomics Sarah

181

Current topics in bioenergetics: Structure, biogenesis, and assembly of energy transducing enzyme systems. Volume 15  

SciTech Connect

This book contains 11 chapters. The chapter titles are: Structure of NADH-Ubiquinone Reductase (Complex I); Structure of the Succinate-Ubiquinone Oxidoreductase (Complex II); Structure of Mitochondrial Ubiquinol-Cytochrome-c Redutase (Complex III); Structure of Cytochrome-c Oxidase; Evolution of a Regulatory Enzyme: Cytochrome-c Oxidase (Complex IV); The Assembly of F/sub 1/F/sub 0/-ATPase in Escherichia coli; Biogenesis of Mitochondrial Energy Transducing Complexes; Biogenesis of Mammalian Mitochondria; Structure and Biogenesis of Chloroplast Coupling Factor (CF/sub 0/CF/sub 1/)-ATPase; Mitochondrial Gene Products; and Overview: Bioenergetics between Chemistry, Genetics, and Physics.

Lee, C.P.

1987-01-01

182

Postexercise whole body heat stress additively enhances endurance training-induced mitochondrial adaptations in mouse skeletal muscle.  

PubMed

A recent study demonstrated that heat stress induces mitochondrial biogenesis in C2C12 myotubes, thereby implying that heat stress may be an effective treatment to enhance endurance training-induced mitochondrial adaptations in skeletal muscle. However, whether heat stress actually induces mitochondrial adaptations in skeletal muscle in vivo is unclear. In the present study, we report the novel findings that 1) whole body heat stress produced by exposure of ICR mice to a hot environment (40°C, 30 min/day, 5 days/wk, 3 wk) induced mitochondrial adaptations such as increased mitochondrial enzyme activity (citrate synthase and 3-hydroxyacyl CoA dehydrogenase) and respiratory chain protein content (complexes I-V) in skeletal muscle in vivo and 2) postexercise whole body heat stress additively enhanced endurance training-induced mitochondrial adaptations (treadmill running, 25 m/min, 30 min/day, 5 days/wk, 3 wk). Moreover, to determine the candidate mechanisms underlying mitochondrial adaptations, we investigated the acute effects of postexercise whole body heat stress on the phosphorylation status of cellular signaling cascades that subsequently induce mitochondrial gene transcription. We found that whole body heat stress boosted the endurance exercise-induced phosphorylation of p38 MAPK, increased the phosphorylation status of p70S6K, a biomarker of mammalian target of rapamycin complex 1 activity, and unexpectedly dephosphorylated AMP-activated protein kinase and its downstream target acetyl-CoA carboxylase in skeletal muscle. Our present observations suggest that heat stress can act as an effective postexercise treatment. Heat stress treatment appeared to be clinically beneficial for people who have difficulty participating in sufficient exercise training, such as the elderly, injured athletes, and patients. PMID:25080501

Tamura, Yuki; Matsunaga, Yutaka; Masuda, Hiroyuki; Takahashi, Yumiko; Takahashi, Yuki; Terada, Shin; Hoshino, Daisuke; Hatta, Hideo

2014-10-01

183

Binding of Yeast Frataxin to the Scaffold for Fe-S Cluster Biogenesis, Isu*  

E-print Network

Binding of Yeast Frataxin to the Scaffold for Fe-S Cluster Biogenesis, Isu* Received, a conserved iron-binding protein of the mitochondrial matrix, thought to supply iron for formation of Fe biogenesis and interaction with Isu while altering neither iron binding nor oligomerization. Our results

Craig, Elizabeth A

184

Exercise?Induced growth hormone during acute sleep deprivation  

PubMed Central

Abstract The effect of acute (24?h) sleep deprivation on exercise?induced growth hormone (GH) and insulin?like growth factor?1 (IGF?1) was examined. Ten men (20.6 ± 1.4 years) completed two randomized 24?h sessions including a brief, high?intensity exercise bout following either a night of sleep (SLEEP) or (24?h) sleep deprivation (SLD). Anaerobic performance (mean power [MP], peak power [PP], minimum power [MinP], time to peak power [TTPP], fatigue index, [FI]) and total work per sprint [TWPS]) was determined from four maximal 30?sec Wingate sprints on a cycle ergometer. Self?reported sleep 7 days prior to each session was similar between SLEEP and SLD sessions (7.92 ± 0.33 vs. 7.98 ± 0.39 h, P =0.656, respectively) and during the actual SLEEP session in the lab, the total amount of sleep was similar to the 7 days leading up to the lab session (7.72 ± 0.14 h vs. 7.92 ± 0.33 h, respectively) (P =0.166). No differences existed in MP, PP, MinP, TTPP, FI, TWPS, resting GH concentrations, time to reach exercise?induced peak GH concentration (TTP), or free IGF?1 between sessions. GH area under the curve (AUC) (825.0 ± 199.8 vs. 2212.9 ± 441.9 ?g/L*min, P <0.01), exercise?induced peak GH concentration (17.8 ± 3.7 vs. 39.6 ± 7.1 ?g/L, P <0.01) and ?GH (peak GH – resting GH) (17.2 ± 3.7 vs. 38.2 ± 7.3 ?g/L, P <0.01) were significantly lower during the SLEEP versus SLD session. Our results indicate that the exercise?induced GH response was significantly augmented in sleep?deprived individuals. PMID:25281616

Ritsche, Kevin; Nindl, Bradly C.; Wideman, Laurie

2014-01-01

185

Extreme sports: extreme physiology. Exercise-induced pulmonary oedema.  

PubMed

We report five patients who presented to an on-site medical team with concurrent haemoptysis and shortness of breath at a recent triathlon event. After initial management in the field, three of the five patients were transported to hospital via ambulance for further management, resulting in patients with haemoptysis and dyspnoea being 17 times more likely to require hospital transport. It is important to consider the differential diagnoses for this presentation, particularly exercise-induced pulmonary oedema. PMID:23911030

Ma, Joyce Lok Gee; Dutch, Martin John

2013-08-01

186

A case of mite-ingestion-associated exercise- induced anaphylaxis mimicking wheat-dependent exercise-induced anaphylaxis.  

PubMed

We present a case of mite-ingestion-associated exercise-induced anaphylaxis mimicking wheat-dependent exercise-induced anaphylaxis (WDEIA). A 17-year-old boy was referred for an episode of anaphylaxis while jogging, 1.5 h after having eaten okonomiyaki (a Japanese pancake). Laboratory measures revealed a slightly elevated specific immunoglobulin E (IgE) antibody against omega-5 gliadin (0.41 kUA/l) and a marked elevation of specific IgE antibody against house-dust mite, Dermatophagoides farinae (142 kUA/l). A detailed interview revealed that, in spite of the referring doctor's advice to discontinue postprandial exercises, he continued his jogging routine after consuming foods containing wheat and also that his younger brother, who had mild intermittent asthma, had suffered a mild asthma attack 2 h after eating the same food. We therefore examined the okonimiyaki mix, which had been stored for several months after opening the package until this episode, under a microscope, and we found an abundant number of live mites, D. farinae. Finally, a diagnosis of mite-ingestion-associated exercise-induced anaphylaxis was made. This clinical entity should be excluded when making a diagnosis of WDEIA. PMID:23921625

Adachi, Yoko S; Itazawa, Toshiko; Okabe, Yoshie; Higuchi, Osamu; Ito, Yasunori; Adachi, Yuichi

2013-01-01

187

Relative abundance of the human mitochondrial transcription system and distinct roles for h-mtTFB1 and h-mtTFB2 in mitochondrial biogenesis and gene expression  

Microsoft Academic Search

Human mitochondrial transcription requires the bacteriophage-related RNA polymerase, POLRMT, the mtDNA-binding protein, h-mtTFA\\/TFAM, and two transcription factors\\/rRNA methyltransferases, h-mtTFB1 and h-mtTFB2. Here, we determined the steady-state levels of these core transcription components and examined the consequences of purposeful elevation of h-mtTFB1 or h-mtTFB2 in HeLa cells. On a per molecule basis, we find an »6-fold excess of POLRMT to mtDNA

Justin Cotney; Zhibo Wang; Gerald S. Shadel

2007-01-01

188

Identification of Coa2 as an assembly factor for cytochrome c oxidase biogenesis1 Fabien Pierrel, Oleh Khalimonchuk, Paul A. Cobine and Dennis R. Winge*3  

E-print Network

).7 The biogenesis of CcO, occurring within the IM, commences with the mitochondrial8 synthesis of the Cox1 subunit1 Identification of Coa2 as an assembly factor for cytochrome c oxidase biogenesis1 2 Fabien with three mitochondrial encoded subunits (Cox1-Cox3) forming the core enzyme embedded4 within

Paris-Sud XI, Université de

189

A time to reap, a time to sow: mitophagy and biogenesis in cardiac pathophysiology.  

PubMed

Balancing mitophagy and mitochondrial biogenesis is essential for maintaining a healthy population of mitochondria and cellular homeostasis. Coordinated interplay between these two forces that govern mitochondrial turnover plays an important role as an adaptive response against various cellular stresses that can compromise cell survival. Failure to maintain the critical balance between mitophagy and mitochondrial biogenesis or homeostatic turnover of mitochondria results in a population of dysfunctional mitochondria that contribute to various disease processes. In this review we outline the mechanics and relationships between mitophagy and mitochondrial biogenesis, and discuss the implications of a disrupted balance between these two forces, with an emphasis on cardiac physiology. This article is part of a Special Issue entitled "Mitochondria: From Basic Mitochondrial Biology to Cardiovascular Disease". PMID:25444712

Andres, Allen M; Stotland, Aleksandr; Queliconi, Bruno B; Gottlieb, Roberta A

2015-01-01

190

The Curious Question of Exercise-Induced Pulmonary Edema  

PubMed Central

The question of whether pulmonary edema develops during exercise on land is controversial. Yet, the development of pulmonary edema during swimming and diving is well established. This paper addresses the current controversies that exist in the field of exercise-induced pulmonary edema on land and with water immersion. It also discusses the mechanisms by which pulmonary edema can develop during land exercise, swimming, and diving and the current gaps in knowledge that exist. Finally, this paper discusses how these fields can continue to advance and the areas where clinical knowledge is lacking. PMID:21660232

Bates, Melissa L.; Farrell, Emily T.; Eldridge, Marlowe W.

2011-01-01

191

Strenuous Exercise Induced Syncope Due to Coronary Artery Anomaly  

PubMed Central

Coronary artery anomalies are among the neglected topics in cardiology. Anomalous origin of the left main coronary artery from the right sinus of valsalva is a rare coronary anomaly observed in 0.15% of patients. During exercise, the distended aorta and pulmonary artery with increased blood flow may squeeze the Left Main Coronary Artery (LMCA) between them. Even though arrhythmias are common causes of syncope, one should also think about aberrant coronary artery in the patients with syncope of unexplained origin. Patients experiencing exercise induced syncope accompanied by symptoms of coronary ischemia (typically: chest pain, ischemic findings on ECG, and raised cardiac markers) should be referred to diagnostic coronary angiography. PMID:25177677

Yavuz, Veysel; Cetin, Nurulah; Tuncer, Esref; Dalgic, Onur; Taskin, Ugur; Bilge, Ali Riza; Tikiz, Hakan

2014-01-01

192

Mitoribosomal regulation of OXPHOS biogenesis in plants  

PubMed Central

The ribosome filter hypothesis posits that ribosomes are not simple non-selective translation machines but may also function as regulatory elements in protein synthesis. Recent data supporting ribosomal filtering come from plant mitochondria where it has been shown that translation of mitochondrial transcripts encoding components of oxidative phosphorylation complexes (OXPHOS) and of mitoribosomes can be differentially affected by alterations in mitoribosomes. The biogenesis of mitoribosome was perturbed by silencing of a gene encoding a small-subunit protein of the mitoribosome in Arabidopsis thaliana. As a consequence, the mitochondrial OXPHOS and ribosomal transcripts were both upregulated, but only the ribosomal proteins were oversynthesized, while the OXPHOS subunits were actually depleted. This finding implies that the heterogeneity of plant mitoribosomes found in vivo could contribute to the functional selectivity of translation under distinct conditions. Furthermore, global analysis indicates that biogenesis of OXPHOS complexes in plants can be regulated at different levels of mitochondrial and nuclear gene expression, however, the ultimate coordination of genome expression occurs at the complex assembly level. PMID:24634672

Janska, Hanna; Kwasniak, Malgorzata

2014-01-01

193

Second Place -Resident Basic Science Award 1995 Mitochondrial role in hair cell survival after injury  

E-print Network

biogenesis in hair cell survival after injury was evaluated by inhibiting mitochondrial protein synthesiswith biogenesis is involved in cellular responses to injury. They suggest that mitochondrial function may regulateSecond Place - Resident Basic Science Award 1995 Mitochondrial role in hair cell survival after

Rubel, Edwin

194

NAMPT regulates mitochondria biogenesis via NAD metabolism and calcium binding proteins during skeletal muscle contraction  

PubMed Central

[Purpose] The purpose of this study was to investigate the effect that muscle contraction induced NAD metabolism via NAMPT has on mitochondrial biogenesis. [Methods] Primary skeletal muscle cells were isolated from the gastrocnemius in C57BL/6 mice. The muscle cells were stimulated by electrical current at 1Hz for 3 minutes in conditions of normal or NAD metabolism related inhibitor treatment. NAD/NADH level, Sirt1 and mitochondria biogenesis related signal factor’s changes were examined in normal or NAD metabolism related inhibitor treated cells. [Results] Electrical stimulation (ES) induced muscle contractions significantly increased NAD/NADH levels, NAMPT inhibitor FK-866 inhibited ES-induced NAD formation, which caused SIRT1 expression and PGC-1? deacetylation to decrease. Moreover, NAMPT inhibition decreased mitochondrial biogenesis related mRNA, COX-1 and Tfam levels. Along with AMPK inhibitor, compound C decreases SIRT1 expression, PGC-1? deacetylation and muscle contraction induced mitochondrial biogenesis related mRNA increment. These results indicated that the AMPK-NAMPT signal is a key player for muscle contraction induced SIRT1 expression and PGC-1? deacetylation, which influences mitochondrial biogenesis. Inhibition of the AMPK upregulator, Camkk?, STO-609 decreased AMPK phosphorylation and SIRT1 expression but did not decrease PGC-1? deacetylation. However, CAMKII inhibition via AIP decreased PGC-1? deacetylation. [Conclusion] In conclusion, the results indicate that NAMPT plays an important role in NAD metabolism and mitochondrial biogenesis. However, mitochondrial biogenesis is also controlled by different calcium binding protein signals including Camkk? and CAMKII. [Keyword] Muscle contraction, NAD metabolism, SIRT1, PGC-1 ?, mitochondria biogenesis. PMID:25566462

Kim, Jeong Seok; Yoon, Chung-Su; Park, Dae Ryoung

2014-01-01

195

Molecular Genetics of Mitochondrial Disorders  

ERIC Educational Resources Information Center

Mitochondrial respiratory chain (RC) disorders (RCDs) are a group of genetically and clinically heterogeneous diseases because of the fact that protein components of the RC are encoded by both mitochondrial and nuclear genomes and are essential in all cells. In addition, the biogenesis, structure, and function of mitochondria, including DNA…

Wong, Lee-Jun C.

2010-01-01

196

Biogenesis of nuclear bodies.  

PubMed

The nucleus is unique amongst cellular organelles in that it contains a myriad of discrete suborganelles. These nuclear bodies are morphologically and molecularly distinct entities, and they host specific nuclear processes. Although the mode of biogenesis appears to differ widely between individual nuclear bodies, several common design principles are emerging, particularly, the ability of nuclear bodies to form de novo, a role of RNA as a structural element and self-organization as a mode of formation. The controlled biogenesis of nuclear bodies is essential for faithful maintenance of nuclear architecture during the cell cycle and is an important part of cellular responses to intra- and extracellular events. PMID:21068152

Dundr, Miroslav; Misteli, Tom

2010-12-01

197

Mitochondrial biogenesis: The Tom and Tim machine  

Microsoft Academic Search

Translocation of precursor proteins into mitochondria depends on loosely assembled protein complexes in the outer and inner membranes. Recent studies indicate that dynamic interactions of subcomplexes and cooperation with molecular chaperones drive key steps in protein import.

Nikolaus Pfanner; Michiel Meijer

1997-01-01

198

Familial Paroxysmal Exercise-Induced Dystonia: Atypical Presentation of Autosomal Dominant GTP-Cyclohydrolase 1 Deficiency  

ERIC Educational Resources Information Center

Paroxysmal exercise-induced dystonia (PED) is one of the rarer forms of paroxysmal dyskinesia, and can occur in sporadic or familial forms. We report a family (male index case, mother and maternal grandfather) with autosomal dominant inheritance of paroxysmal exercise-induced dystonia. The dystonia began in childhood and was only ever induced…

Dale, Russell C.; Melchers, Anna; Fung, Victor S. C.; Grattan-Smith, Padraic; Houlden, Henry; Earl, John

2010-01-01

199

Overexpression of the Mitochondrial T3 Receptor Induces Skeletal Muscle Atrophy during Aging  

Microsoft Academic Search

In previous studies, we characterized a new hormonal pathway involving a mitochondrial T3 receptor (p43) acting as a mitochondrial transcription factor. In in vitro and in vivo studies, we have shown that p43 increases mitochondrial transcription and mitochondrial biogenesis. In addition, p43 overexpression in skeletal muscle stimulates mitochondrial respiration and induces a shift in metabolic and contractile features of muscle

François Casas; Laurence Pessemesse; Stéphanie Grandemange; Pascal Seyer; Olivier Baris; Naïg Gueguen; Christelle Ramonatxo; Florence Perrin; Gilles Fouret; Laurence Lepourry; Gérard Cabello; Chantal Wrutniak-Cabello; Jose A. L. Calbet

2009-01-01

200

Knee proprioception after exercise-induced muscle damage.  

PubMed

The purpose of the present study was to investigate whether exercise-induced quadriceps muscle damage affects knee proprioception such as joint position sense (JPS), force sense and the threshold to detect passive movement (TTDPM). Fourteen young men performed sets of eccentric quadriceps contractions at a target of 60% of the maximal concentric peak torque until exhaustion; the exercise was interrupted whenever the subject could not complete two sets. Muscle soreness, JPS, the TTDPM and force sense were examined before the exercise as well as one, 24, 48, 72 and 96 h after exercise. The results were compared using one-way repeated-measure ANOVA. Plasma CK activity, collected at the same times, was analyzed by the Friedman's test to discriminate differences between baseline values and each of the other assessment moments (p<0.05). Relative to the proprioception assessment, JPS at 30 and 70 degrees of knee flexion and force sense were significantly decreased up to 48 h, whereas TTDPM decreased significantly at only one hour and 24 h after exercise, at 30 and 70 degrees of the knee flexion, respectively. The results allow the conclusion that eccentric exercise leading to muscle damage alters joint proprioception, suggesting that there might be impairment in the intrafusal fibres of spindle muscles and in the tendon organs. PMID:20301043

Torres, R; Vasques, J; Duarte, J A; Cabri, J M H

2010-06-01

201

Diaphragmatic breathing reduces exercise-induced oxidative stress.  

PubMed

Diaphragmatic breathing is relaxing and therapeutic, reduces stress, and is a fundamental procedure of Pranayama Yoga, Zen, transcendental meditation and other meditation practices. Analysis of oxidative stress levels in people who meditate indicated that meditation correlates with lower oxidative stress levels, lower cortisol levels and higher melatonin levels. It is known that cortisol inhibits enzymes responsible for the antioxidant activity of cells and that melatonin is a strong antioxidant; therefore, in this study, we investigated the effects of diaphragmatic breathing on exercise-induced oxidative stress and the putative role of cortisol and melatonin hormones in this stress pathway. We monitored 16 athletes during an exhaustive training session. After the exercise, athletes were divided in two equivalent groups of eight subjects. Subjects of the studied group spent 1?h relaxing performing diaphragmatic breathing and concentrating on their breath in a quiet place. The other eight subjects, representing the control group, spent the same time sitting in an equivalent quite place. Results demonstrate that relaxation induced by diaphragmatic breathing increases the antioxidant defense status in athletes after exhaustive exercise. These effects correlate with the concomitant decrease in cortisol and the increase in melatonin. The consequence is a lower level of oxidative stress, which suggests that an appropriate diaphragmatic breathing could protect athletes from long-term adverse effects of free radicals. PMID:19875429

Martarelli, Daniele; Cocchioni, Mario; Scuri, Stefania; Pompei, Pierluigi

2011-01-01

202

Mechanisms of Isometric Exercise-Induced Hypoalgesia in Young and Older Adults.  

E-print Network

??Pain reduction following exercise (exercise-induced hypoalgesia; EIH) is well-established in young adults. Specific to isometric exercise, the greatest EIH follows low intensity contractions held for… (more)

Lemley, Kathy J.

2014-01-01

203

Exercise-induced increments in plasma levels of propranolol and noradrenaline.  

PubMed Central

Exercise-induced changes in the plasma levels of propranolol and noradrenaline were determined in nine volunteers. Total plasma propranolol levels were increased during submaximal treadmill exercise, with exercise-induced increments of 13 +/- 4% at 4 h after the last dose, 18 +/- 7% at 9 h and 41 +/- 5% at 16 h. Exercise-induced increments in plasma propranolol were observed after single as well as repeated doses. During exercise, increments in plasma propranolol were correlated temporally with changes in plasma noradrenaline. Exercise-induced increments in plasma noradrenaline were greater during propranolol administration than during placebo periods. The changes in plasma propranolol concentration during exercise may reflect a redistribution of propranolol at its site(s) of action. PMID:6661342

Hurwitz, G A; Webb, J G; Walle, T; Bai, S A; Daniell, H B; Gourley, L; Boyd Loadholt, C; Gaffney, T E

1983-01-01

204

Peroxisome Biogenesis and Function  

PubMed Central

Peroxisomes are small and single membrane-delimited organelles that execute numerous metabolic reactions and have pivotal roles in plant growth and development. In recent years, forward and reverse genetic studies along with biochemical and cell biological analyses in Arabidopsis have enabled researchers to identify many peroxisome proteins and elucidate their functions. This review focuses on the advances in our understanding of peroxisome biogenesis and metabolism, and further explores the contribution of large-scale analysis, such as in sillco predictions and proteomics, in augmenting our knowledge of peroxisome function In Arabidopsis. PMID:22303249

Kaur, Navneet; Reumann, Sigrun; Hu, Jianping

2009-01-01

205

Effect of exercise-induced hyperventilation on airway resistance and cycling endurance  

Microsoft Academic Search

The purpose of the present study was to investigate the effect of exercise induced hyperventilation and hypocapnia on airway\\u000a resistance (R\\u000a aw), and to try to answer the question whether a reduction of R\\u000a aw is a mechanism contributing to the increase of endurance time associated with a reduction of exercise induced hyperventilation\\u000a as for example has been observed after

J. Kohl; E. A. Koller; M. Brandenberger; M. Cardenas; U. Boutellier

1997-01-01

206

Effects of cold water immersion on the symptoms of exercise-induced muscle damage  

Microsoft Academic Search

Cryotherapy is an effective treatment for acute sports injury to soft tissue, although the effect of cryotherapy on exercise-induced muscle damage is unclear. The aim of this study was to assess the effects of cold water immersion on the symptoms of exercise-induced muscle damage following strenuous eccentric exercise. After performing a bout of damage-inducing eccentric exercise (eight sets of five

ROGER ESTON; DANIEL PETERS

1999-01-01

207

Cytochrome c Oxidase Biogenesis: New levels of Regulation  

PubMed Central

Summary Eukaryotic cytochrome c oxidase (COX), the last enzyme of the mitochondrial respiratory chain, is a multimeric enzyme of dual genetic origin, whose assembly is a complicated and highly regulated process. COX displays a concerted accumulation of its constitutive subunits. Data obtained from studies performed with yeast mutants indicate that most catalytic core unassembled subunits are post-translationally degraded. Recent data obtained in the yeast Saccharomyces cerevisiae have revealed another contribution to the stoichiometric accumulation of subunits during COX biogenesis targeting subunit 1 or Cox1p. Cox1p is a mitochondrially encoded catalytic subunit of COX which acts as a seed around which the full complex is assembled. A regulatory mechanism exists by which Cox1p synthesis is controlled by the availability of its assembly partners. The unique properties of this regulatory mechanism offer a means to catalyze multiple-subunit assembly. New levels of COX biogenesis regulation have been recently proposed. For example, COX assembly and stability of the fully assembled enzyme depend on the presence in the mitochondrial compartments of two partners of the oxidative phosphorylation system, the mobile electron carrier cytochrome c and the mitochondrial ATPase. The different mechanisms of regulation of COX assembly are reviewed and discussed. PMID:18465791

Fontanesi, Flavia; Soto, Ileana C.; Barrientos, Antoni

2008-01-01

208

Role of Surf1 in heme recruitment for bacterial COX biogenesis.  

PubMed

Biogenesis of the mitochondrial cytochrome c oxidase (COX) is a highly complex process involving subunits encoded both in the nuclear and the organellar genome; in addition, a large number of assembly factors participate in this process. The soil bacterium Paracoccus denitrificans is an interesting alternative model for the study of COX biogenesis events because the number of chaperones involved is restricted to an essential set acting in the metal centre formation of oxidase, and the high degree of sequence homology suggests the same basic mechanisms during early COX assembly. Over the last years, studies on the P. denitrificans Surf1 protein shed some light on this important assembly factor as a heme a binding protein associated with Leigh syndrome in humans. Here, we summarise our current knowledge about Surf1 and its role in heme a incorporation events during bacterial COX biogenesis. This article is part of a Special Issue entitled: Biogenesis/Assembly of Respiratory Enzyme Complexes. PMID:21945856

Hannappel, Achim; Bundschuh, Freya A; Ludwig, Bernd

2012-06-01

209

Compensation for a Defective Interaction of the Hsp70 Ssq1 with the Mitochondrial Fe-S Cluster Scaffold Isu*  

E-print Network

, Wisconsin 53706 Ssq1, a specialized yeast mitochondrial Hsp70, plays a critical role in the biogenesisCompensation for a Defective Interaction of the Hsp70 Ssq1 with the Mitochondrial Fe-S Cluster in targeting substrates for Hsp70 binding (4­7). Biogenesis of Fe-S clusters is a critical step

Craig, Elizabeth A

210

Exercise training and immune crosstalk in breast cancer microenvironment: exploring the paradigms of exercise-induced immune modulation and exercise-induced myokines  

PubMed Central

Observational research suggests that exercise may reduce the risk of breast cancer and improve survival. One proposed mechanism for the protective effect of aerobic exercise related to cancer risk and outcomes, but has not been examined definitively, is the immune response to aerobic exercise. Two prevailing paradigms are proposed. The first considers the host immune response as modifiable by aerobic exercise training. This exercise-modulated immune-tumor crosstalk in the mammary microenvironment may alter the balance between tumor initiation and progression versus tumor suppression. The second paradigm considers the beneficial role of exercise-induced, skeletal muscle-derived cytokines, termed “myokines”. These myokines exert endocrine-like effects on multiple organs, including the mammary glands. In this systematic review, we i) define the role of macrophages and T-cells in breast cancer initiation and progression; ii) address the two paradigms that support exercise-induced immunomodulation; iii) systematically assessed the literature for exercise intervention that assessed biomarkers relevant to both paradigms in human intervention trials of aerobic exercise training, in healthy women and women with breast cancer; iv) incorporated pre-clinical animal studies and non-RCTs for background discussion of putative mechanisms, through which aerobic exercise training modulates the immunological crosstalk, or the myokine-tumor interaction in the tumor microenvironment; and v) speculated on the potential biomarkers and mechanisms that define an exercise-induced, anti-tumor “signature”, with a view toward developing relevant biomarkers for future aerobic exercise intervention trials. PMID:25360210

Goh, Jorming; Niksirat, Negin; Campbell, Kristin L

2014-01-01

211

MicroRNA-23a has minimal effect on endurance exercise-induced adaptation of mouse skeletal muscle.  

PubMed

Skeletal muscles contain several subtypes of myofibers that differ in contractile and metabolic properties. Transcriptional control of fiber-type specification and adaptation has been intensively investigated over the past several decades. Recently, microRNA (miRNA)-mediated posttranscriptional gene regulation has attracted increasing attention. MiR-23a targets key molecules regulating contractile and metabolic properties of skeletal muscle, such as myosin heavy-chains and peroxisome proliferator-activated receptor gamma, coactivator 1 alpha (PGC-1?). In the present study, we analyzed the skeletal muscle phenotype of miR-23a transgenic (miR-23a Tg) mice to explore whether forced expression of miR-23a affects markers of mitochondrial content, muscle fiber composition, and muscle adaptations induced by 4 weeks of voluntary wheel running. When compared with wild-type mice, protein markers of mitochondrial content, including PGC-1?, and cytochrome c oxidase complex IV (COX IV), were significantly decreased in the slow soleus muscle, but not the fast plantaris muscle of miR-23a Tg mice. There was a decrease in type IId/x fibers only in the soleus muscle of the Tg mice. Following 4 weeks of voluntary wheel running, there was no difference in the endurance exercise capacity as well as in several muscle adaptive responses including an increase in muscle mass, capillary density, or the protein content of myosin heavy-chain IIa, PGC-1?, COX IV, and cytochrome c. These results show that miR-23a targets PGC-1? and regulates basal metabolic properties of slow but not fast twitch muscles. Elevated levels of miR-23a did not impact on whole body endurance capacity or exercise-induced muscle adaptations in the fast plantaris muscle. PMID:24756198

Wada, Shogo; Kato, Yoshio; Sawada, Shuji; Aizawa, Katsuji; Park, Jong-Hoon; Russell, Aaron P; Ushida, Takashi; Akimoto, Takayuki

2015-02-01

212

Oral contraceptive use and exercise-induced muscle damage and recovery  

Microsoft Academic Search

Endogenous estrogen appears to attenuate muscle damage in animals; however, similar evidence in humans is not as strong. This investigation tested the hypothesis that women taking oral contraceptives, thereby having higher exogenous estrogen levels, would be more susceptible to damage or have an attenuated recovery from exercise-induced muscle damage. Muscle damage in women taking combined estrogen and progesterone oral contraceptives

Kathleen J Savage; Priscilla M Clarkson

2002-01-01

213

High protein diet maintains glucose production during exercise-induced energy deficit: a controlled trial  

Technology Transfer Automated Retrieval System (TEKTRAN)

Inadequate energy intake induces changes in endogenous glucose production (GP) to preserve muscle mass. Whether addition provision of dietary protein modulates GP response to energy deficit is unclear. The objective was to determine whether exercise-induced energy deficit effects on glucose metaboli...

214

Update on Exercise-Induced Asthma. A Report of the Olympic Exercise Asthma Summit Conference.  

ERIC Educational Resources Information Center

Summarizes results from the Olympic Exercise Asthma Summit Conference, offering the latest on identifying and managing exercise-induced asthma (EIA). Concludes that effective pharmacologic and nonpharmacologic treatment is available, but EIA is underrecognized and underdiagnosed. Physicians should look for it in all patients, including school…

Storms, William W.; Joyner, David M.

1997-01-01

215

Exercise induced bronchospasm in Ghana: differences in prevalence between urban and rural schoolchildren  

Microsoft Academic Search

BACKGROUND: As more developing countries adopt a westernised style of living, an increase in the prevalence of asthma can be expected to occur in these areas. A study was undertaken to establish the normal response to exercise in Ghanaian children and to use these normal values to determine the prevalence of exercise induced bronchospasm (EIB) in urban rich (UR), urban

E. O. Addo Yobo; A. Custovic; S. C. Taggart; A. P. Asafo-Agyei; A. Woodcock

1997-01-01

216

Green tea extract supplementation protects from exercise-induced oxidative damage in healthy men  

Microsoft Academic Search

The purpose of this study was to evaluate the effects of chronic (four-week) green tea extract supplementation in combination with strength training on selected blood markers of oxidative stress and muscular damage after acute exercise in previously untrained men. We hypothesized that GTE supplementation would elevate antioxidant potential and attenuate exercise-induced oxidative stress and muscular damage. Thirty five male students

Ewa Jówko; Jaroslaw Sacharuk; Bozena Balasi?ska; Piotr Ostaszewski; Malgorzata Charmas; Robert Charmas

217

The Roles of Testosterone and Alpha-Amylase in Exercise-Induced Sexual Arousal in Women  

E-print Network

The Roles of Testosterone and Alpha-Amylase in Exercise-Induced Sexual Arousal in Women Lisa Dawn-report questionnaire, and genital arousal was measured by a vaginal photoplethysmograph. Testosterone and a-amylase (a. There was a significant increase in a-amylase across the study in the exercise condition, but not in the no

Meston, Cindy

218

Exercise-induced ischemic preconditioning detected by sequential exercise stress tests: A meta-analysis.  

PubMed

Exercise-induced ischemic preconditioning (IPC) can be assessed with the second exercise stress test during sequential testing. Exercise-induced IPC is defined as the time to 1?mm ST segment depression (STD), the rate-pressure product (RPP) at 1?mm STD, the maximal ST depression and the rate-pressure product at peak exercise. The purpose of this meta-analysis is to validate the parameters used to assess exercise-induced IPC in the scientific community. A literature search was performed using electronic database. The main key words were limited to human studies, which were (a) ischemic preconditioning, (b) warm-up phenomenon, and (c) exercise. Meta-analyses were performed on the study-specific mean difference between the clinical measures obtained in the two consecutive stress tests (second minus first test score). Random effect models were fitted with inverse variance weighting to provide greater weight to studies with larger sample size and more precise estimates. The search resulted in 309 articles of which 34 were included after revision (1053 patients). Results are: (a) time to 1?mm ST segment depression increased by 91?s (95% confidence interval (CI): 75-108), p?exercise-induced ischemic preconditioning in sequential stress testing. The results of this first meta-analysis on the sequential stress test confirm what is presented in the literature by independent studies on exercise-induced ischemic preconditioning. From now on, the results could be used in further research to set standardized parameters to assess the phenomenon. PMID:23983070

Lalonde, François; Poirier, Paul; Sylvestre, Marie-Pierre; Arvisais, Denis; Curnier, Daniel

2015-01-01

219

GTP is required for iron-sulfur cluster biogenesis in mitochondria.  

PubMed

Iron-sulfur (Fe-S) cluster biogenesis in mitochondria is an essential process and is conserved from yeast to humans. Several proteins with Fe-S cluster cofactors reside in mitochondria, including aconitase [4Fe-4S] and ferredoxin [2Fe-2S]. We found that mitochondria isolated from wild-type yeast contain a pool of apoaconitase and machinery capable of forming new clusters and inserting them into this endogenous apoprotein pool. These observations allowed us to develop assays to assess the role of nucleotides (GTP and ATP) in cluster biogenesis in mitochondria. We show that Fe-S cluster biogenesis in isolated mitochondria is enhanced by the addition of GTP and ATP. Hydrolysis of both GTP and ATP is necessary, and the addition of ATP cannot circumvent processes that require GTP hydrolysis. Both in vivo and in vitro experiments suggest that GTP must enter into the matrix to exert its effects on cluster biogenesis. Upon import into isolated mitochondria, purified apoferredoxin can also be used as a substrate by the Fe-S cluster machinery in a GTP-dependent manner. GTP is likely required for a common step involved in the cluster biogenesis of aconitase and ferredoxin. To our knowledge this is the first report demonstrating a role of GTP in mitochondrial Fe-S cluster biogenesis. PMID:18029354

Amutha, Boominathan; Gordon, Donna M; Gu, Yajuan; Lyver, Elise R; Dancis, Andrew; Pain, Debkumar

2008-01-18

220

Pharmacological approaches to restore mitochondrial function  

PubMed Central

Mitochondrial dysfunction is not only a hallmark of rare inherited mitochondrial disorders, but is also implicated in age-related diseases, including those that affect the metabolic and nervous system, such as type 2 diabetes and Parkinson’s disease. Numerous pathways maintain and/or restore proper mitochondrial function, including mitochondrial biogenesis, mitochondrial dynamics, mitophagy, and the mitochondrial unfolded protein response. New and powerful phenotypic assays in cell-based models, as well as multicellular organisms, have been developed to explore these different aspects of mitochondrial function. Modulating mitochondrial function has therefore emerged as an attractive therapeutic strategy for a range of diseases, which has spurred active drug discovery efforts in this area. PMID:23666487

Andreux, Pénélope A.; Houtkooper, Riekelt H.; Auwerx, Johan

2014-01-01

221

Cellulose biogenesis in Dictyostelium discoideum  

SciTech Connect

Organisms that synthesize cellulose can be found amongst the bacteria, protistans, fungi, and animals, but it is in plants that the importance of cellulose in function (as the major structural constituent of plant cell walls) and economic use (as wood and fiber) can be best appreciated. The structure of cellulose and its biosynthesis have been the subjects of intense investigation. One of the most important insights gained from these studies is that the synthesis of cellulose by living organisms involves much more than simply the polymerization of glucose into a (1{r_arrow}4)-{beta}-linked polymer. The number of glucoses in a polymer (the degree of polymerization), the crystalline form assumed by the glucan chains when they crystallize to form a microfibril, and the dimensions and orientation of the microfibrils are all subject to cellular control. Instead of cellulose biosynthesis, a more appropriate term might be cellulose biogenesis, to emphasize the involvement of cellular structures and mechanisms in controlling polymerization and directing crystallization and deposition. Dictyostelium discoideum is uniquely suitable for the study of cellulose biogenesis because of its amenability to experimental study and manipulation and the extent of our knowledge of its basic cellular mechanisms (as will be evident from the rest of this volume). In this chapter, I will summarize what is known about cellulose biogenesis in D. discoideum, emphasizing its potential to illuminate our understanding both of D. discoideum development and plant cellulose biogenesis.

Blanton, R.L.

1993-12-31

222

Relationship between exercise induced dyspnea and functional capacity with doppler-derived diastolic function’  

PubMed Central

Background Dyspnea is the frequent cause of exercise intolerance and physical inactivity among patients referred for exercise tolerance test. Diastolic dysfunction has shown significant correlation with exercise capacity and exercise induced dyspnea. To find out the frequency of diastolic dysfunction (DD) and the relationships between impaired exercise capacity and exercise induced dyspnea with DD by Doppler-derived indices among patients referred for stress test in a tertiary care hospital of Karachi. Methods For this study 135 consecutive patients who were referred for stress test at our non-invasive lab were screened for eligibility. Patients with valvular pathology, atrial fibrillation (AF) and coronary artery disease (CAD) were excluded. Stress test was performed on treadmill using Bruce protocol. Assessment of diastolic function as determined by trans-mitral flow velocity pattern was carried at baseline and at peak exercise. We evaluated impaired exercise capacity and exercise induced dyspnea using validated Borg Scale among study subjects. Results Study subjects 88% were males, mean age was 46?±?16 years, BMI 27?±?5 kg/m2, prevalence of diabetes mellitus (DM) 15%, hypertension 28% and smoking 21%. Exercise induced DD occurred among 44.6%. Patients with exercise induced DD had lower exercise capacity (9.2 vs. 10.2 METS; p?=?0.04) and higher Borg Scale (5.2 vs. 4.0; p?exercise induced dyspnea and impaired exercise tolerance. Conclusion DD is significantly associated with impaired functional capacity and dyspnea among patients referred for exercise tolerance test. PMID:23587172

2013-01-01

223

Mitochondrial plasticity with exercise training and extreme environments.  

PubMed

Mitochondria form a reticulum in skeletal muscle. Exercise training stimulates mitochondrial biogenesis, yet an emerging hypothesis is that training also induces qualitative regulatory changes. Substrate oxidation, oxygen affinity, and biochemical coupling efficiency may be regulated differentially with training and exposure to extreme environments. Threshold training doses inducing mitochondrial upregulation remain to be elucidated considering fitness level. PMID:25062000

Boushel, Robert; Lundby, Carsten; Qvortrup, Klaus; Sahlin, Kent

2014-10-01

224

Cell, Vol. 98, 115124, July 9, 1999, Copyright 1999 by Cell Press Mechanisms Controlling Mitochondrial  

E-print Network

Mitochondrial Biogenesis and Respiration through the Thermogenic Coactivator PGC-1 More recently, there has been. The uncoupling proteins (UCPs) are small,Facolta di Medicina e Chirurgia intramembranous mitochondrial proteins (Fleury et al., 1997; Gi- Mitochondrial number and function are altered in re- meno et al., 1997

225

A 5 cytosine binding pocket in Puf3p specifies regulation of mitochondrial mRNAs  

E-print Network

metallochaperone involved in the biogenesis of the mitochondrial respiratory complex (7, 11, 12). ThusA 5 cytosine binding pocket in Puf3p specifies regulation of mitochondrial mRNAs Deyu Zhua,1RNAs that encode proteins with mitochondrial function. Here we eluci- date the structural basis of that specificity

Wickens, Marv

226

UNVEILING THE METABOLIC NETWORK UNDERLYING MITOCHONDRIAL AND NUCLEAR METABOLISM IN A MODEL DIFFERENTIATING STEM CELL  

E-print Network

, mitochondrial biogenesis. #12;iv Acknowledgement I would like to express my appreciation to Dr. Vasu AppannaUNVEILING THE METABOLIC NETWORK UNDERLYING MITOCHONDRIAL AND NUCLEAR METABOLISM IN A MODEL of Thesis Titre de la thèse UNVEILING THE METABOLIC NETWORK UNDERLYING MITOCHONDRIAL AND NUCLEAR METABOLISM

Appanna, Vasu

227

The efficiency of mitochondrial electron transport chain is increased in the long-lived mrg19  

E-print Network

despite high oxygen consumption) was explained as a result of mitochondrial biogenesis, which providesThe efficiency of mitochondrial electron transport chain is increased in the long-lived mrg19 of mitochondrial functionality is a key deter- minant of longevity in several organisms. In particular, reduced

Babu, M. Madan

228

p53 Improves Aerobic Exercise Capacity and Augments Skeletal Muscle Mitochondrial DNA Content  

E-print Network

of mitochondrial biogenesis. As p53 did not affect baseline cardiac function or inotropic reserve, we focusedp53 Improves Aerobic Exercise Capacity and Augments Skeletal Muscle Mitochondrial DNA Content Joon regulates mitochondrial function and its deletion markedly diminishes exercise capacity, but the underlying

Leary, Scot

229

A Chemical Screen Probing the Relationship between Mitochondrial Content and Cell Size  

E-print Network

mechanism that governs mitochondrial biogenesis and turnover. Citation: Kitami T, Logan DJ, Negri J, HasakaA Chemical Screen Probing the Relationship between Mitochondrial Content and Cell Size Toshimori obscure. To systematically identify molecular probes and pathways that control mitochondrial abundance, we

Mootha, Vamsi K.

230

Overlapping Specificities of the Mitochondrial Cytochrome c and c1 Heme Lyases*S  

E-print Network

previously only as a mitochondrial biogenesis factor. Based on the func- tional interaction of Cyc2pOverlapping Specificities of the Mitochondrial Cytochrome c and c1 Heme Lyases*S Received by signaling mitochondrial status (2). Their distinctive feature is the covalent attachment of the prosthetic

Meier, Iris

231

1985 Elsevier Science Publishers B.V. (Biomedical Division) Achievements and Perspectives of Mitochondrial Research  

E-print Network

of Mitochondrial Research Volume II: Biogenesis, E. Quagliariello et al. editors 99 GENOMIC ORGANIZATION AND TRANSCRIPTION OF MITOCHONDRIAL MAXICIRCLE DNA IN TRYPANOSOMID PROTOZOA L. SIMPSON, A. M. SIMPSON, V. DE LA CRUZ of California, Los Angeles, CA 90024 (USA) INTRODUCTION Comparative analysis of mitochondrial genomes from

Simpson, Larry

232

Oxidative Phosphorylation: Synthesis of Mitochondrially Encoded Proteins and Assembly of Individual Structural  

E-print Network

and the adaptive increases in their abundance that accom- pany mitochondrial biogenesis require the de novoChapter 10 Oxidative Phosphorylation: Synthesis of Mitochondrially Encoded Proteins and Assembly by five multimeric protein complexes (I­V) embedded within the inner mitochondrial membrane, in a process

Shoubridge, Eric

233

Polyphenols in Exercise Performance and Prevention of Exercise-Induced Muscle Damage  

PubMed Central

Although moderate physical exercise is considered an essential component of a healthy lifestyle that leads the organism to adapt itself to different stresses, exercise, especially when exhaustive, is also known to induce oxidative stress, inflammation, and muscle damage. Many efforts have been carried out to identify dietary strategies or micronutrients able to prevent or at least attenuate the exercise-induced muscle damage and stress. Unfortunately most studies have failed to show protection, and at the present time data supporting the protective effect of micronutrients, as antioxidant vitamins, are weak and trivial. This review focuses on those polyphenols, present in the plant kingdom, that have been recently suggested to exert some positive effects on exercise-induced muscle damage and oxidative stress. In the last decade flavonoids as quercetin, catechins, and other polyphenols as resveratrol have caught the scientists attention. However, at the present time drawing a clear and definitive conclusion seems to be untimely. PMID:23983900

Hrelia, Silvana

2013-01-01

234

Deciphering protein-protein interactions during the biogenesis of cytochrome c oxidase from Paracoccus denitrificans.  

PubMed

Biogenesis of the mitochondrial cytochrome c oxidase (COX) is a complex process due to its numerous subunits encoded by two genomes, as well as the localization of redox centers deep within the membrane. Here, we have assessed the biogenesis of the homologous aa3 -type oxidase of the soil bacterium Paracoccus denitrificans. First, protein partners were analyzed using various membrane solubilization strategies to show interactions between COX and CtaG, a chaperone implicated in CuB site metallation. Using an unbiased MS approach after immunological pull-down from untreated or cross-linked membranes, we then extend our view towards a hypothetical 'biogenesis complex' by identifying two further metal-inserting chaperones, Surf1c and Sco, together with enzymes catalyzing heme a synthesis. Our study also tentatively supports previous speculation regarding the existence of a predominantly co-translational mechanism for cofactor insertion during COX biogenesis. PMID:25420759

Gurumoorthy, Priya; Ludwig, Bernd

2015-02-01

235

Role of positively charged transmembrane segments in the insertion and assembly of mitochondrial  

E-print Network

Role of positively charged transmembrane segments in the insertion and assembly of mitochondrial) The biogenesis of membrane oligomeric complexes is an intricate process that requires the insertion and assembly hydrophobic TM domains from the translocation site into the lipid bilayer. The biogenesis of membrane

Meier, Iris

236

Dietary supplementation of Vitamin E protects heart tissue from exercise-induced oxidant stress  

Microsoft Academic Search

Exhaustive endurance exercise in adult female albino rats (C-Ex) increased the generation of free radicals (R ·) in the myocardium, probably through enhanced oxidative mechanisms. Free radical mediated lipid peroxidation measured in the form of tissue MDA content also increased in C-Ex animals, suggesting the exercise-induced oxidative stress in these animals. Dietary supplementation of Vit E, for a period of

Charles T. Kumar; Veera K. Reddy; M. Prasad; K. Thyagaraju; P. Reddanna

1992-01-01

237

Intermittent pneumatic compression effect on eccentric exercise-induced swelling, stiffness, and strength loss  

Microsoft Academic Search

Objective: The purpose was to determine if intermittent pneumatic compression (IPC) affects muscle swelling, stiffness, and strength loss resulting from eccentric exercise-induced injury of the elbow flexors. We hypothesized that the compression would decrease swelling and stiffness. Design: Repeated measures design with a before-after trial comparison within each day. Setting: Conducted at a university Somatic Dysfunction Laboratory. Subjects: Twenty-two college

Gary S. Chleboun; John N. Howell; Heather L. Baker; Tina N. Ballard; Jennifer L. Graham; Holly L. Hallman; Lori E. Perkins; Jonathan H. Schauss; Robert R. Conatser

1995-01-01

238

Effect of restricted blood flow on exercise-induced hormone changes in healthy men  

Microsoft Academic Search

To test the influence of the accumulation of metabolites on exercise-induced hormone responses, plasma concentrations of\\u000a cortisol, growth hormone (GH), insulin, testosterone, thyrotropin (TSH), free thyroxine (fT4) and triiodothyronine (T3) were compared during exercise performed under normal conditions (control) and under conditions of restricted blood flow\\u000a of exercising leg muscles (ischaemia) in nine healthy young men. Blood supply was reduced

Mehis Viru; Eva Jansson; Atko Viru; Carl Johan Sundberg

1998-01-01

239

Causes of differences in exercise-induced changes of base excess and blood lactate  

Microsoft Academic Search

It has been concluded from comparisons of base excess (BE) and lactic acid (La) concentration changes in blood during exercise-induced\\u000a acidosis that more H+ than La? leave the muscle and enter interstitial fluid and blood. To examine this, we performed incremental cycle tests in 13 untrained\\u000a males and measured acid–base status and [La] in arterialized blood, plasma, and red cells

Dieter Böning; Carola Klarholz; Bärbel Himmelsbach; Matthias Hütler; Norbert Maassen

2007-01-01

240

Exercised-induced increase in lipid peroxidation parameters in amenorrhelc female athletes  

Microsoft Academic Search

Objective: To determine plasma lipid peroxidation parameters in eumenorrheic and amenorrheic athletes and to evaluate differences in their response to exercise-induced oxidative stress. In female athletes, intense physical exercise has been shown to be associated with an increased occurrence of menstrual dysfunction with lower levels of E2. Recently, a protective role has been demonstrated for estrogens as free radical scavengers.Design:

Stacey Ayres; Janine Baer; M. T. Ravi Subbiah

1998-01-01

241

Exercise-Induced Reduction in Obesity and Insulin Resistance in Women: a Randomized Controlled Trial  

Microsoft Academic Search

Objectives: To determine the effects of equivalent diet- or exercise-induced weight loss and exercise without weight loss on subcutaneous fat, visceral fat, and insulin sensitivity in obese women.Research Methods and Procedures: Fifty-four premenopausal women with abdominal obesity [waist circumference 110.1 ± 5.8 cm (mean ± SD)] (BMI 31.3 ± 2.0 kg\\/m2) were randomly assigned to one of four groups: diet

Robert Ross; Ian Janssen; Jody Dawson; Ann-Marie Kungl; Jennifer L. Kuk; Suzy L. Wong; Thanh-Binh Nguyen-Duy; SoJung Lee; Katherine Kilpatrick; Robert Hudson

2004-01-01

242

Genotyping of exercise-induced collapse in Labrador retrievers using an allele-specific PCR.  

PubMed

Exercise-induced collapse (EIC) is an autosomal recessive disorder in Labrador retrievers. In this study, an allele-specific PCR was developed to detect the point mutation G767T in exon 6 of canine DNM1, previously shown to be responsible for canine EIC. Of 133 Labrador retrievers tested in Japan, 6 (4.5%) were homozygous (EIC) and 50 (37.6%) were heterozygous (carriers) for the G767T mutation. PMID:22104507

Takanosu, Masamine; Mori, Hirokazu; Suzuki, Hiroetsu; Suzuki, Katsushi

2012-07-01

243

Frequency of food-dependent, exercise-induced anaphylaxis in Japanese junior-high-school students  

Microsoft Academic Search

Background: Food-dependent, exercise-induced anaphylaxis (FEIAn) is classified among the physical allergies. The pathophysiology of FEIAn remains unknown, as does the frequency of FEIAn in the general population. Objective: We sought to study the epidemiology of FEIAn, especially its frequency in junior-high-school students in Yokohama, Japan. Methods: A questionnaire asking about the occurrence of FEIAn in school students was sent to

Yukoh Aihara; Yuriko Takahashi; Takeshi Kotoyori; Toshihiro Mitsuda; Reiko Ito; Michiko Aihara; Zenro Ikezawa; Shumpei Yokota

2001-01-01

244

Ultra-endurance exercise induces stress and inflammation and affects circulating hematopoietic progenitor cell function.  

PubMed

Although amateur sports have become increasingly competitive within recent decades, there are as yet few studies on the possible health risks for athletes. This study aims to determine the impact of ultra-endurance exercise-induced stress on the number and function of circulating hematopoietic progenitor cells (CPCs) and hematological, inflammatory, clinical, metabolic, and stress parameters in moderately trained amateur athletes. Following ultra-endurance exercise, there were significant increases in leukocytes, platelets, interleukin-6, fibrinogen, tissue enzymes, blood lactate, serum cortisol, and matrix metalloproteinase-9. Ultra-endurance exercise did not influence the number of CPCs but resulted in a highly significant decline of CPC functionality after the competition. Furthermore, Epstein-Barr virus was seen to be reactivated in one of seven athletes. The link between exercise-induced stress and decline of CPC functionality is supported by a negative correlation between cortisol and CPC function. We conclude that ultra-endurance exercise induces metabolic stress and an inflammatory response that affects not only mature hematopoietic cells but also the function of the immature hematopoietic stem and progenitor cell fraction, which make up the immune system and provide for regeneration. PMID:25438993

Stelzer, I; Kröpfl, J M; Fuchs, R; Pekovits, K; Mangge, H; Raggam, R B; Gruber, H-J; Prüller, F; Hofmann, P; Truschnig-Wilders, M; Obermayer-Pietsch, B; Haushofer, A C; Kessler, H H; Mächler, P

2014-12-01

245

Food-dependent exercise-induced anaphylaxis due to wheat in a young woman.  

PubMed

Food Dependent Exercise-Induced Allergy is a rare condition. However, the occurrence of anaphylaxis is increasing especially in young people. The diagnosis of anaphylaxis is based on clinical criteria and can be supported by laboratory tests such as serum tryptase and positive skin test results for specific IgE to potential triggering allergens. Anaphylaxis prevention needs strict avoidance of confirmed relevant allergen. Food-exercise challenge test may be an acceptable method for diagnosis of Food Dependent Exercise-Induced Allergy and dietary elimination of food is recommended to manage it. In this study, a 32 year-old woman visited the allergy clinic with a history of several episodes of hives since 11 years ago and 3 life-threatening attacks of anaphylaxis during the previous 6 months. The onsets of majority of these attacks were due to physical activity after breakfast. On Blood RAST test, the panel of common food Allergens was used and she had positive test only to wheat flour. On skin prick tests for common food allergens she showed a 6 millimeter wheal with 14 mm flare to Wheat Extract. The rest of allergens were negative.The patient was diagnosed as wheat-dependent exercise-induced, and all foods containing wheat were omitted from her diet. In this report we emphasized on the importance of careful history taking in anaphylaxis diagnosis. PMID:23454785

Ahanchian, Hamid; Farid, Reza; Ansari, Elham; Kianifar, Hamid Reza; Jabbari Azad, Farahzad; Jafari, Seyed Ali; Purreza, Reza; Noorizadeh, Shadi

2013-03-01

246

The effect of sports specialization on musculus quadriceps function after exercise-induced muscle damage.  

PubMed

The primary aim of the present study was to examine the effect of eccentric exercise-induced (100 submaximal eccentric contractions at an angular velocity of 60° s?¹, with 20-s rest intervals) muscle damage on peripheral and central fatigue of quadriceps muscle in well-trained long-distance runners, sprint runners, volleyball players, and untrained subjects. We found that (i) indirect symptoms of exercise-induced muscle damage (prolonged decrease in maximal voluntary contraction, isokinetic concentric torque, and electrically induced (20 Hz) torque) were most evident in untrained subjects, while there were no significant differences in changes of muscle soreness and plasma creatine kinase 48 h after eccentric exercise between athletes and untrained subjects; (ii) low-frequency fatigue was greater in untrained subjects and volleyball players than in sprint runners and long-distance runners; (iii) in all subjects, electrically induced (100 Hz) torque decreased significantly by about 20%, while central activation ratio decreased significantly by about 8% in untrained subjects and sprint runners, and by about 3%-5% in long-distance runners and volleyball players. Thus, trained subjects showed greater resistance to exercise-induced muscle damage for most markers, and long-distance runners had no advantage over sprint runners or volleyball players. PMID:22050132

Skurvydas, Albertas; Brazaitis, Marius; Venck?nas, Tomas; Kamandulis, Sigitas; Stanislovaitis, Aleksas; Zuoza, Aurelijus

2011-12-01

247

Organelle biogenesis and interorganellar connections  

PubMed Central

Membrane contact sites (MCSs) allow the exchange of molecules and information between organelles, even when their membranes cannot fuse directly. In recent years, a number of functions have been attributed to these contacts, highlighting their critical role in cell homeostasis. Although inter-organellar connections typically involve the endoplasmic reticulum (ER), we recently reported the presence of a novel MCSs between melanosomes and mitochondria. Melanosome-mitochondrion contacts appear mediated by fibrillar bridges resembling the protein tethers linking mitochondria and the ER, both for their ultrastructural features and the involvement of Mitofusin 2. The frequency of these connections correlates spatially and timely with melanosome biogenesis, suggesting a functional link between the 2 processes and in general that organelle biogenesis in the secretory pathway requires interorganellar crosstalks at multiple steps. Here, we summarize the different functions attributed to MCSs, and discuss their possible relevance for the newly identified melanosome-mitochondrion liaison. PMID:25346798

Daniele, Tiziana; Schiaffino, Maria Vittoria

2014-01-01

248

Peroxisome biogenesis in Saccharomyces cerevisiae  

Microsoft Academic Search

The observation that peroxisomes ofSaccharomyces cerevisiae can be induced by oleic acid has opened the possibility to investigate the biogenesis of these organelles in a biochemically and genetically well characterized organism. Only few enzymes have been identified as peroxisomal proteins inSaccharomyces cerevisiae so far; the three enzymes involved in ß-oxidation of fatty acids, enzymes of the glyoxylate cycle, catalase A

Wolf-H. Kunau; Andreas Hartig

1992-01-01

249

Essential role of Isd11 in mitochondrial iron–sulfur cluster synthesis on Isu scaffold proteins  

PubMed Central

Mitochondria are indispensable for cell viability; however, major mitochondrial functions including citric acid cycle and oxidative phosphorylation are dispensable. Most known essential mitochondrial proteins are involved in preprotein import and assembly, while the only known essential biosynthetic process performed by mitochondria is the biogenesis of iron–sulfur clusters (ISC). The components of the mitochondrial ISC-assembly machinery are derived from the prokaryotic ISC-assembly machinery. We have identified an essential mitochondrial matrix protein, Isd11 (YER048w-a), that is found in eukaryotes only. Isd11 is required for biogenesis of cellular Fe/S proteins and thus is a novel subunit of the mitochondrial ISC-assembly machinery. It forms a complex with the cysteine desulfurase Nfs1 and is required for formation of an Fe/S cluster on the Isu scaffold proteins. We conclude that Isd11 is an indispensable eukaryotic component of the mitochondrial machinery for biogenesis of Fe/S proteins. PMID:16341089

Wiedemann, Nils; Urzica, Eugen; Guiard, Bernard; Müller, Hanne; Lohaus, Christiane; Meyer, Helmut E; Ryan, Michael T; Meisinger, Chris; Mühlenhoff, Ulrich; Lill, Roland; Pfanner, Nikolaus

2006-01-01

250

Mitochondrial Dysfunction in Cancer  

PubMed Central

A mechanistic understanding of how mitochondrial dysfunction contributes to cell growth and tumorigenesis is emerging beyond Warburg as an area of research that is under-explored in terms of its significance for clinical management of cancer. Work discussed in this review focuses less on the Warburg effect and more on mitochondria and how dysfunctional mitochondria modulate cell cycle, gene expression, metabolism, cell viability, and other established aspects of cell growth and stress responses. There is increasing evidence that key oncogenes and tumor suppressors modulate mitochondrial dynamics through important signaling pathways and that mitochondrial mass and function vary between tumors and individuals but the significance of these events for cancer are not fully appreciated. We explore the interplay between key molecules involved in mitochondrial fission and fusion and in apoptosis, as well as in mitophagy, biogenesis, and spatial dynamics of mitochondria and consider how these distinct mechanisms are coordinated in response to physiological stresses such as hypoxia and nutrient deprivation. Importantly, we examine how deregulation of these processes in cancer has knock on effects for cell proliferation and growth. We define major forms of mitochondrial dysfunction and address the extent to which the functional consequences of such dysfunction can be determined and exploited for cancer diagnosis and treatment. PMID:24350057

Boland, Michelle L.; Chourasia, Aparajita H.; Macleod, Kay F.

2013-01-01

251

Integrated pathways of parkin control over mitochondrial maintenance - relevance to Parkinson's disease pathogenesis.  

PubMed

Mitochondrial dysfunction and oxidative stress are considered among the main molecular mechanisms implicated in Parkinson's disease (PD) pathogenesis. Here, we focus on the deficiency of PARK2 and its product parkin, which is relevant to both familial and sporadic PD pathogenesis. Parkin emerges as an important regulator of processes that maintain mitochondrial quality. We focus on the parkin-dependent aspects of mitochondrial biogenesis, including mtDNA replication, transcription, mitophagy, mitochondrial fusion, fission, and transport. We discuss possible underlying molecular mechanisms, exerted by parkin in cooperation with other mitochondrial maintenance factors such as TFAM, PGC-1alpha, mortalin, HSP70/HSC70 and LRPPRC, all of them implicated in PD pathogenesis. We review numerous models of lipopolysaccharide toxicity that demonstrate how mitochondrial biogenesis and mitophagy are induced simultaneously to cope with mitochondrial dysfunction. The spatial and temporal interdependence of mitochondrial quality pathways underscores the importance of an integrative approach for future studies. PMID:23823983

Gaweda-Walerych, Katarzyna; Zekanowski, Cezary

2013-01-01

252

MitoTimer: a novel protein for monitoring mitochondrial turnover in the heart.  

PubMed

Mitochondrial quality control refers to the coordinated cellular systems involved in maintaining a population of healthy mitochondria. In addition to mitochondrial protein chaperones (Hsp10, Hsp60, and others) and proteases (Lon, AAA proteases) needed for refolding or degrading individual proteins, mitochondrial integrity is maintained through the regulation of protein import via the TOM/TIM complex and protein redistribution across the network via fusion and fission and through mitophagy and biogenesis, key determinants of mitochondrial turnover. A growing number of studies point to the importance of mitochondrial dynamics (fusion/fission) and mitochondrial autophagy in the heart. Mitochondrial biogenesis must keep pace with mitophagy in order to maintain a stable number of mitochondria. In this review, we will discuss the use of MitoTimer as a tool to monitor mitochondrial turnover. PMID:25479961

Gottlieb, Roberta A; Stotland, Aleksandr

2014-12-01

253

The Effect of RNA Interference Down-regulation of RNA Editing 3 -Terminal Uridylyl Transferase (TUTase) 1 on Mitochondrial  

E-print Network

of the mitochondrial RNA editing TUTase 1 by RNA interference had profound effects on kinetoplast biogenesis (TUTase) 1 on Mitochondrial de Novo Protein Synthesis and Stability of Respiratory Complexes with a decline in the levels of the assembled mitochondrial respiratory complexes III and IV, and also cyanide

Simpson, Larry

254

Exercise-induced hemostatic alterations are detectable by rotation thrombelastography (ROTEM): A marathon study.  

PubMed

Rotation thrombelastography (ROTEM) provides a whole blood assay that allows the assessment of plasmic- and platelet-related hemostasis in a single-step procedure. In our current study, we focused on the capability of the method to detect hemostatic alterations induced by physical exercise, enrolling 33 healthy participants of the Dusseldorf Marathon 2006. Venous blood drawn immediately before and after finishing the marathon was analyzed by a rotational thrombelastograph (Pentapharm, Munich, Germany). On initiation of blood coagulation by recalcification, standard ROTEM parameters were determined. Comparison of the results obtained before and after the physical exercise was performed using the Student t test for paired samples. As a result, the mean clotting time (CT) determined from blood samples obtained immediately after the marathon was significantly shorter (662.9 + or - 67.8 seconds vs 505.6 + or - 97.3 seconds, P = .002) and the mean maximal clot firmness was significantly broader (48.4 +/- 6.6 mm vs 51.5 +/- 4.5 mm, P = .0004) when compared to results obtained before the physical exercise. Differences between mean clot formation times (CFTs; 280.6 + 96 seconds vs 270.4 + or - 73.8 seconds) and mean alpha angles (45.9 degrees + or - 8 degrees vs 47.8 degrees + or - 5.8 degrees ) before and after the marathon were not statistically significant. Remarkably, some participants showed opposed results, particularly prolongation of CT and narrowing of maximum clot firmness (MCF). Our study demonstrates that ROTEM is sensitive to exercise-induced hemostatic alterations. The method appears to be capable of detecting even distinct changes in hemostasis in a single-step procedure. Further analyses are needed to clarify which hemostasis parameters influence ROTEM results and which ROTEM results are independent predictors of exercise-induced alterations of plasmic and platelet function. This might help to explain interindividual differences in exercise-induced alterations of hemostasis. PMID:19696040

Sucker, Christoph; Zotz, Rainer B; Senft, Beate; Scharf, Rudiger E; Kröger, Knut; Erbel, Raimund; Möhlenkamp, Stefan

2010-10-01

255

Relation among exercise-induced ventricular arrhythmias, myocardial ischemia, and viability late after acute myocardial infarction.  

PubMed

This study assesses the relation between exercise-induced ventricular arrhythmia (VA) and scintigraphic markers of myocardial ischemia and viability in patients referred for exercise stress testing late after acute myocardial infarction. We studied 171 patients (144 men, age 57 +/- 10 years) with resting wall motion abnormalities by exercise stress testing in conjunction with methoxyisobutyl isonitrile (MIBI) single-photon emission computed tomography at a mean of 4.1 years after myocardial infarction. Ischemia was defined as reversible perfusion abnormalities. Myocardial viability was considered in myocardial segments with resting wall motion abnormalities in the presence of normal perfusion, a reversible defect or a fixed defect with regional MIBI uptake > or = 50% of maximal uptake. Exercise-induced VA occurred in 46 patients (27%). Patients with VA had a higher prevalence of infarct-related artery stenosis (43 [93%] vs 93 [74%], p < 0.01), peri-infarction ischemia (32 [70%] vs 54 [43%], p < 0.005), and ischemia in > or = 2 vascular regions (20 [43%] vs 27 [22%], p < 0.01) than patients without VA. Reversible defects were detected in 39 of 97 dyssynergic segments (40%) in patients with versus 40 of 248 dyssynergic segments (16%) in patients without VA (p < 0.0001). In dyssynergic segments without reversible perfusion abnormalities, the percent resting MIBI uptake was > or = 50% in 39 of 58 segments (67%) in patients with versus 63% in 131 of 208 segments in patients without VA (p = NS). The percentage of viable segments was 80% and 69% in patients with and without VA, respectively (p < 0.05). It is concluded that patients with exercise-induced VA late after myocardial infarction have a higher prevalence of ischemia in the peri-infarction zone and in multivessel distribution. Myocardial ischemia in the dyssynergic myocardium appears to be a major mechanism underlying the occurrence of VA in these patients. PMID:11018190

Elhendy, A; Sozzi, F B; van Domburg, R T; Bax, J J; Geleijnse, M L; Roelandt, J R

2000-10-01

256

Loss of functional endothelial connexin40 results in exercise-induced hypertension in mice.  

PubMed

During activity, coordinated vasodilation of microcirculatory networks with upstream supply vessels increases blood flow to skeletal and cardiac muscles and reduces peripheral resistance. Endothelial dysfunction in humans attenuates activity-dependent vasodilation, resulting in exercise-induced hypertension in otherwise normotensive individuals. Underpinning activity-dependent hyperemia is an ascending vasodilation in which the endothelial gap junction protein, connexin (Cx)40, plays an essential role. Because exercise-induced hypertension is proposed as a forerunner to clinical hypertension, we hypothesized that endothelial disruption of Cx40 function in mice may create an animal model of this condition. To this end, we created mice in which a mutant Cx40T152A was expressed alongside wildtype Cx40 selectively in the endothelium. Expression of the Cx40T152A transgene in Xenopus oocytes and mouse coronary endothelial cells in vitro impaired both electric and chemical conductance and acted as a dominant-negative against wildtype Cx40, Cx43, and Cx45, but not Cx37. Endothelial expression of Cx40T152A in Cx40T152ATg mice attenuated ascending vasodilation, without effect on radial coupling through myoendothelial gap junctions. Using radiotelemetry, Cx40T152ATg mice showed an activity-dependent increase in blood pressure, which was significantly greater than in wildtype mice, but significantly less than in chronically hypertensive, Cx40knockout mice. The increase in heart rate with activity was also greater than in wildtype or Cx40knockout mice. We conclude that the endothelial Cx40T152A mutation attenuates activity-dependent vasodilation, producing a model of exercise-induced hypertension. These data highlight the importance of endothelial coupling through Cx40 in regulating blood pressure during activity. PMID:25547341

Morton, Susan K; Chaston, Daniel J; Howitt, Lauren; Heisler, Jillian; Nicholson, Bruce J; Fairweather, Stephen; Bröer, Stefan; Ashton, Anthony W; Matthaei, Klaus I; Hill, Caryl E

2015-03-01

257

BDNF Expression in Perirhinal Cortex is Associated with Exercise-Induced Improvement in Object Recognition Memory  

PubMed Central

Physical exercise induces widespread neurobiological adaptations and improves learning and memory. Most research in this field has focused on hippocampus-based spatial tasks and changes in brain-derived neurotrophic factor (BDNF) as a putative substrate underlying exercise-induced cognitive improvements. Chronic exercise can also be anxiolytic and causes adaptive changes in stress reactivity. The present study employed a perirhinal cortex-dependent object recognition task as well as the elevated plus maze to directly test for interactions between the cognitive and anxiolytic effects of exercise in male Long Evans rats. Hippocampal and perirhinal cortex tissue was collected to determine whether the relationship between BDNF and cognitive performance extends to this non-spatial and non-hippocampal-dependent task. We also examined whether the cognitive improvements persisted once the exercise regimen was terminated. Our data indicate that 4 weeks of voluntary exercise every-other-day improved object recognition memory. Importantly, BDNF expression in the perirhinal cortex of exercising rats was strongly correlated with object recognition memory. Exercise also decreased anxiety-like behavior, however there was no evidence to support a relationship between anxiety-like behavior and performance on the novel object recognition task. There was a trend for a negative relationship between anxiety-like behavior and hippocampal BDNF. Neither the cognitive improvements nor the relationship between cognitive function and perirhinal BDNF levels persisted after 2 weeks of inactivity. These are the first data demonstrating that region-specific changes in BDNF protein levels are correlated with exercise-induced improvements in non-spatial memory, mediated by structures outside the hippocampus and are consistent with the theory that, with regard to object recognition, the anxiolytic and cognitive effects of exercise may be mediated through separable mechanisms. PMID:20601027

Hopkins, Michael E.; Bucci, David J.

2010-01-01

258

Phosphatidylserine Decarboxylase 1 (Psd1) Promotes Mitochondrial Fusion by Regulating the Biophysical Properties of the Mitochondrial Membrane and Alternative Topogenesis of Mitochondrial Genome Maintenance Protein 1 (Mgm1)*  

PubMed Central

Non–bilayer-forming lipids such as cardiolipin, phosphatidic acid, and phosphatidylethanolamine (PE) are proposed to generate negative membrane curvature, promoting membrane fusion. However, the mechanism by which lipids regulate mitochondrial fusion remains poorly understood. Here, we show that mitochondrial-localized Psd1, the key yeast enzyme that synthesizes PE, is required for proper mitochondrial morphology and fusion. Yeast cells lacking Psd1 exhibit fragmented and aggregated mitochondria with impaired mitochondrial fusion during mating. More importantly, we demonstrate that a reduction in PE reduces the rate of lipid mixing during fusion of liposomes with lipid compositions reflecting the mitochondrial membrane. This suggests that the mitochondrial fusion defect in the ?psd1 strain could be due to the altered biophysical properties of the mitochondrial membrane, resulting in reduced fusion kinetics. The ?psd1 strain also has impaired mitochondrial activity such as oxidative phosphorylation and reduced mitochondrial ATP levels which are due to a reduction in mitochondrial PE. The loss of Psd1 also impairs the biogenesis of s-Mgm1, a protein essential for mitochondrial fusion, further exacerbating the mitochondrial fusion defect of the ?psd1 strain. Increasing s-Mgm1 levels in ?psd1 cells markedly reduced mitochondrial aggregation. Our results demonstrate that mitochondrial PE regulates mitochondrial fusion by regulating the biophysical properties of the mitochondrial membrane and by enhancing the biogenesis of s-Mgm1. While several proteins are required to orchestrate the intricate process of membrane fusion, we propose that specific phospholipids of the mitochondrial membrane promote fusion by enhancing lipid mixing kinetics and by regulating the action of profusion proteins. PMID:23045528

Chan, Eliana Y. L.; McQuibban, G. Angus

2012-01-01

259

Effect of Antioxidant Supplementation on Exercise-Induced Cardiac Troponin Release in Cyclists: A Randomized Trial  

PubMed Central

Background Cardiac troponin is the biochemical gold standard to diagnose acute myocardial infarction. Interestingly however, elevated cardiac troponin concentrations are also frequently observed during and after endurance-type exercise. Oxidative stress associated with prolonged exercise has been proposed to contribute to cardiac troponin release. Therefore, the aim of this study was to assess the effect of 4 week astaxanthin supplementation (a potent cartenoid antioxidant) on antioxidant capacity and exercise-induced cardiac troponin release in cyclists. Methods Thirty-two well-trained male cyclists (age 25±5, weight 73±7 kg, maximum O2 uptake 60±5 mL·kg?1·min?1, Wmax 5.4±0.5 W·kg?1; mean ± SD) were repeatedly subjected to a laboratory based standardized exercise protocol before and after 4 weeks of astaxanthin (20 mg/day), or placebo supplementation in a double-blind randomized manner. Blood samples were obtained at baseline, at 60 min of cycling and immediately post-exercise (? 120 min). Results The pre-supplementation cycling trial induced a significant rise of median cardiac troponin T concentrations from 3.2 (IQR 3.0–4.2) to 4.7 ng/L (IQR 3.7–6.7), immediately post-exercise (p<0.001). Four weeks of astaxanthin supplementation significantly increased mean basal plasma astaxanthin concentrations from non-detectable values to 175±86 µg·kg?1. However, daily astaxanthin supplementation had no effect on exercise-induced cardiac troponin T release (p?=?0.24), as measured by the incremental area under the curve. Furthermore, the elevation in basal plasma astaxanthin concentrations was not reflected in changes in antioxidant capacity markers (trolox equivalent antioxidant capacity, uric acid, and malondialdehyde). Markers of inflammation (high-sensitivity C-reactive protein) and exercise-induced skeletal muscle damage (creatine kinase) were equally unaffected by astaxanthin supplementation. Conclusion Despite substantial increases in plasma astaxanthin concentrations, astaxanthin supplementation did not improve antioxidant capacity in well-trained cyclists. Accordingly, exercise-induced cardiac troponin T concentrations were not affected by astaxanthin supplementation. Trial registration ClinicalTrials.gov NCT01241877 PMID:24260184

Haenen, Guido R.; Bast, Aalt; van Loon, Luc J. C.; van Dieijen-Visser, Marja P.; Meex, Steven J.R.

2013-01-01

260

Exercise-induced acute renal failure associated with ibuprofen, hydrochlorothiazide, and triamterene.  

PubMed

Nonsteroidal anti-inflammatory drugs predispose to acute renal failure in conditions associated with decreased RBF. Such conditions include advanced age, hypertension, chronic renal insufficiency, diuretic use, and any condition decreasing effective circulating volume. Strenuous exercise also causes marked reductions in RBF. The patient discussed developed severe acute renal failure after strenuous exercise and therapeutic doses of ibuprofen and hydrochlorothiazide-triamterene. Urinalysis showed a nephritic sediment with red blood cell casts. Renal biopsy showed acute tubular necrosis and arteriolar nephrosclerosis. Although exercise-associated acute renal failure is uncommon, susceptible patients with exercise-induced renal ischemia and prostaglandin inhibition may develop this complication. PMID:7579049

Sanders, L R

1995-06-01

261

Mitochondrial Dynamics: Functional Link with Apoptosis  

PubMed Central

Mitochondria participate in a variety of physiologic processes, such as ATP production, lipid metabolism, iron-sulfur cluster biogenesis, and calcium buffering. The morphology of mitochondria changes dynamically due to their frequent fusion and division in response to cellular conditions, and these dynamics are an important constituent of apoptosis. The discovery of large GTPase family proteins that regulate mitochondrial dynamics, together with novel insights into the role of mitochondrial fusion and fission in apoptosis, has provided important clues to understanding the molecular mechanisms of cellular apoptosis. In this paper, we briefly summarize current knowledge of the role of mitochondrial dynamics in apoptosis and cell pathophysiology in mammalian cells. PMID:22536251

Otera, Hidenori; Mihara, Katsuyoshi

2012-01-01

262

The Ubiquitin-Proteasome System Regulates Mitochondrial Intermembrane Space Proteins  

PubMed Central

Mitochondrial precursor proteins are synthesized in the cytosol and subsequently imported into mitochondria. The import of mitochondrial intermembrane space proteins is coupled with their oxidative folding and governed by the mitochondrial intermembrane space import and assembly (MIA) pathway. The cytosolic steps that precede mitochondrial import are not well understood. We identified a role for the ubiquitin-proteasome system in the biogenesis of intermembrane space proteins. Interestingly, the function of the ubiquitin-proteasome system is not restricted to conditions of mitochondrial protein import failure. The ubiquitin-proteasome system persistently removes a fraction of intermembrane space proteins under physiological conditions, acting as a negative regulator in the biogenesis of this class of proteins. Thus, the ubiquitin-proteasome system plays an important role in determining the levels of proteins targeted to the intermembrane space of mitochondria. PMID:23508107

Bragoszewski, Piotr; Gornicka, Agnieszka; Sztolsztener, Malgorzata E.

2013-01-01

263

Evidence for Mitochondrial Respiratory Deficiency in Rat Rhabdomyosarcoma Cells  

PubMed Central

Background Mitochondria can sense signals linked to variations in energy demand to regulate nuclear gene expression. This retrograde signaling pathway is presumed to be involved in the regulation of myoblast proliferation and differentiation. Rhabdomyosarcoma cells are characterized by their failure to both irreversibly exit the cell cycle and complete myogenic differentiation. However, it is currently unknown whether mitochondria are involved in the failure of rhabdomyosarcoma cells to differentiate. Methodology/Principal Findings Mitochondrial biogenesis and metabolism were studied in rat L6E9 myoblasts and R1H rhabdomyosacoma cells during the cell cycle and after 36 hours of differentiation. Using a combination of flow cytometry, polarographic and molecular analyses, we evidenced a marked decrease in the cardiolipin content of R1H cells cultured in growth and differentiation media, together with a significant increase in the content of mitochondrial biogenesis factors and mitochondrial respiratory chain proteins. Altogether, these data indicate that the mitochondrial inner membrane composition and the overall process of mitochondrial biogenesis are markedly altered in R1H cells. Importantly, the dysregulation of protein-to-cardiolipin ratio was associated with major deficiencies in both basal and maximal mitochondrial respiration rates. This deficiency in mitochondrial respiration probably contributes to the inability of R1H cells to decrease mitochondrial H2O2 level at the onset of differentiation. Conclusion/Significance A defect in the regulation of mitochondrial biogenesis and mitochondrial metabolism may thus be an epigenetic mechanism that may contribute to the tumoral behavior of R1H cells. Our data underline the importance of mitochondria in the regulation of myogenic differentiation. PMID:20072609

Jahnke, Vanessa E.; Sabido, Odile; Defour, Aurélia; Castells, Josiane; Lefai, Etienne; Roussel, Damien; Freyssenet, Damien

2010-01-01

264

Effects of supplementation with alpha-lipoic acid on exercise-induced activation of coagulation.  

PubMed

Physical exercise leads to minor activation of blood coagulation, which appears to be balanced by a concomitant activation of the fibrinolytic system. The mechanisms underlying this physiological phenomenon are still unknown. To evaluate the role of oxidative stress for exercise-induced activation of coagulation, we investigated if supplementation with alpha -lipoic acid (LA) as an antioxidant reduces the hemostatic response to exercise. Ten young men (age, 25 +/- 4 years; maximal oxygen consumption [V o 2 max], 61 +/- 6 mL/(kg min) [mean +/- SD]) were subjected to a 1-hour run on a treadmill at a velocity corresponding to an oxygen demand of 75% to 80% of maximum (anaerobic threshold). Exercise testing was repeated in the same subjects after supplementation with LA (1200 mg/d PO) for 10 days. Molecular markers of thrombin (prothrombin fragment 1 + 2, thrombin-antithrombin complexes) and fibrin formation (fibrinopeptide A) as well as markers of the fibrinolytic activity (tissue-plasminogen activator, plasmin-antiplasmin complexes, d -dimers) and of lipid peroxidation (malondialdehyde) were determined before and immediately after exercise. Supplementation therapy with LA had no effect on hemostatic and fibrinolytic variables either at rest or in response to exercise. Likewise, concentrations of malondialdehyde at rest and after exercise were not influenced by LA. In summary, the hemostatic response to exercise is not affected by supplementation with LA in young healthy male individuals. The role of oxidative stress for exercise-induced activation of coagulation has to be defined in further studies. PMID:15931620

Weiss, Claus; Bierhaus, Angelika; Nawroth, Peter P; Bärtsch, Peter

2005-06-01

265

Exercise induced steroid dependent dystonia, ataxia, and alternating hemiplegia associated with epilepsy  

PubMed Central

This paper describes a 20 year old woman with a new combination of neurological impairments in which the motor phenomena were responsive to corticosteroid treatment. She had lifelong moderate learning impairment. A variable ataxia with cerebellar characteristics was present from early life, with early severe exacerbation when seizures were uncontrolled. Atypical absence and simple and complex partial seizures were present from the first year of life and EEG abnormalities were maximal in the right parietal region, concordant with a mild non-specific abnormality of the white matter in the region of the trigone. Episodes of alternating hemiplegia occurred from 11 years, unassociated with seizures. Exercise induced dystonia occurred from the age of 5. After 10-20 minutes walking, her right foot would turn in and the right leg would stiffen, followed by the left and by falling and inability to get up for several minutes. Prednisolone improved her ataxia and was associated with cessation of both seizures and exercise induced dystonia. This adds a new syndrome to the corticosteroid responsive motor disorders associated with epilepsy.?? PMID:9703179

Neville, B; Besag, F; Marsden, C

1998-01-01

266

Protective effects of Radix Pseudostellariae polysaccharides against exercise-induced oxidative stress in male rats.  

PubMed

The main purpose of this study was to examine the effect of Radix Pseudostellariae polysaccharides (RPPs) against swimming exercise-induced oxidative stress in male rats. A total of 40 male Wistar rats were randomized into four groups: the control (C), low-dose RPP supplementation (LRS), medium-dose RPP supplementation (MRS) and high-dose RPP supplementation (HRS) groups. The control group received saline solution and the supplementation groups received different doses of RPPs (100, 200 and 400 mg/kg body weight, respectively). The animals were medicated orally and daily for 28 days. On day 28, the rats were made to swim until exhausted. The exhaustive swimming time and various biochemical parameters, including blood lactate, hemoglobin, catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and malondialdehyde (MDA), were measured. The results showed that RPP supplementation elevates the exercise tolerance and decreases the blood lactate level of rats following exhaustive swimming exercise. RPP supplementation augments the levels of hemoglobin and anti-oxidant enzymes (CAT, SOD and GSH-Px), and effectively decreases the MDA content of the skeletal muscle of rats, which suggests that RPP supplementation has a protective effect against exercise-induced oxidative stress. PMID:23596474

Chen, Zichao; Li, Shanshan; Wang, Xiaoqin; Zhang, Chuan Long

2013-04-01

267

Exercise-induced cardiac fatigue in low and normal birth weight young black adults.  

PubMed

The objective of the study was to compare the change in diastolic function, E/A ratio, in response to prolonged exercise in low birth weight and normal birth weight individuals. Using a case-control study design, 23 students of the University of Zimbabwe College of Health Sciences who had neonatal clinic cards as proof of birth weight were recruited into the study. Measurements of diastolic function, E/A ratio, were obtained using an echocardiogram before and after 75 minutes of exercise. Among the cohort, seven had low birth weight - <2500 g, three female patients and four male patients - and 16 had normal birth weight - six female patients and 10 male patients). The mean age was 20.7±3.3 years. After prolonged exercise for 75 minutes of running on a treadmill, decreases in diastolic function, E/A ratio, were significantly greater in low birth weight than in normal birth weight individuals (0.48±0.27 versus 0.19±0.18 p<0.05, respectively). There was a significant association between low birth weight and exercise-induced cardiac fatigue (the ?2 test p<0.05, odds ratio 4.64, 95% confidence interval 1.19-18.1). We conclude that low birth weight is associated with exercise-induced diastolic dysfunction in young adults. PMID:24713506

Chifamba, Jephat; Mapfumo, Chidochashe; Mawoneke, Dorcas W; Gwaunza, Lenon T; Allen, Larry A; Chinyanga, Herbert M

2015-03-01

268

Proposed new mechanism for food and exercise induced anaphylaxis based on case studies.  

PubMed

We present two cases of food and exercise-induced anaphylaxis (FEIA) in patients with a diagnosis of oral allergy syndrome (OAS) to the implicated foods. Patient A had FEIA attributed to fresh coriander and tomato and Patient B to fresh celery. These food allergens have been implicated in OAS and have structural antigenic similarity to that of birch and/or grass. Both patients' allergies were confirmed by fresh skin prick tests. In both cases, strenuous exercise was antecedent to the systemic anaphylaxis reaction and subsequent ingestion without exercise produced only local symptoms of perioral pruritus. We review the current proposed mechanisms for food and exercise induced anaphylaxis to oral allergens and propose a novel and more biologically plausible mechanism. We hypothesize that the inhibitory effects of exercise on gastric acid secretion decreases the digestion of oral allergens and preserves structural integrity, thereby allowing continued systemic absorption of the allergen whether it be profilins, lipid transfer proteins, or other antigenic determinants. PMID:23509907

Chen, Jennifer Yan Fei; Quirt, Jaclyn; Lee, Kihyuk Jason

2013-01-01

269

Effects of curcumin supplementation on exercise-induced oxidative stress in humans.  

PubMed

The purpose of this study was to investigate the effects of curcumin supplementation on exercise-induced oxidative stress in humans. 10 male participants, ages 26.8±2.0 years (mean±SE), completed 3 trials in a random order: (1) placebo (control), (2) single (only before exercise) and (3) double (before and immediately after exercise) curcumin supplementation trials. Each participant received oral administration of 90?mg of curcumin or the placebo 2h before exercise and immediately after exercise. Each participant walked or ran at 65% of V?2max on a treadmill for 60min. Blood samples were collected pre-exercise, immediately after exercise and 2h after exercise. The concentrations of serum derivatives of reactive oxygen metabolites measured immediately after exercise were significantly higher than pre-exercise values in the placebo trial (308.8±12.9 U. CARR, P<0.05), but not in the single (259.9±17.1 U. CARR) or double (273.6±19.7 U. CARR) curcumin supplementation trials. Serum biological antioxidant potential concentrations measured immediately after exercise were significantly elevated in the single and double curcumin supplementation trials compared with pre-exercise values (P<0.05). These findings indicate that curcumin supplementation can attenuate exercise-induced oxidative stress by increasing blood antioxidant capacity. PMID:24165958

Takahashi, M; Suzuki, K; Kim, H K; Otsuka, Y; Imaizumi, A; Miyashita, M; Sakamoto, S

2014-06-01

270

The endocannabinoid system mediates aerobic exercise-induced antinociception in rats.  

PubMed

Exercise-induced antinociception is widely described in the literature, but the mechanisms involved in this phenomenon are poorly understood. Systemic (s.c.) and central (i.t., i.c.v.) pretreatment with CB? and CB? cannabinoid receptor antagonists (AM251 and AM630) blocked the antinociception induced by an aerobic exercise (AE) protocol in both mechanical and thermal nociceptive tests. Western blot analysis revealed an increase and activation of CB? receptors in the rat brain, and immunofluorescence analysis demonstrated an increase of activation and expression of CB? receptors in neurons of the periaqueductal gray matter (PAG) after exercise. Additionally, pretreatment (s.c., i.t. and i.c.v.) with endocannabinoid metabolizing enzyme inhibitors (MAFP and JZL184) and an anandamide reuptake inhibitor (VDM11) prolonged and intensified this antinociceptive effect. These results indicate that exercise could activate the endocannabinoid system, producing antinociception. Supporting this hypothesis, liquid-chromatography/mass-spectrometry measurements demonstrated that plasma levels of endocannabinoids (anandamide and 2-arachidonoylglycerol) and of anandamide-related mediators (palmitoylethanolamide and oleoylethanolamide) were increased after AE. Therefore, these results suggest that the endocannabinoid system mediates aerobic exercise-induced antinociception at peripheral and central levels. PMID:24148812

Galdino, Giovane; Romero, Thiago R L; Silva, José Felipe P; Aguiar, Daniele C; de Paula, Ana Maria; Cruz, Jader S; Parrella, Cosimo; Piscitelli, Fabiana; Duarte, Igor D; Di Marzo, Vincenzo; Perez, Andrea C

2014-02-01

271

Simulation of Exercise-Induced Syncope in a Heart Model with Severe Aortic Valve Stenosis  

PubMed Central

Severe aortic valve stenosis (AVS) can cause an exercise-induced reflex syncope (RS). The precise mechanism of this syncope is not known. The changes in hemodynamics are variable, including arrhythmias and myocardial ischemia, and one of the few consistent changes is a sudden fall in systemic and pulmonary arterial pressures (suggesting a reduced vascular resistance) followed by a decline in heart rate. The contribution of the cardioinhibitory and vasodepressor components of the RS to hemodynamics was evaluated by a computer model. This lumped-parameter computer simulation was based on equivalent electronic circuits (EECs) that reflect the hemodynamic conditions of a heart with severe AVS and a concomitantly decreased contractility as a long-term detrimental consequence of compensatory left ventricular hypertrophy. In addition, the EECs model simulated the resetting of the sympathetic nervous tone in the heart and systemic circuit during exercise and exercise-induced syncope, the fluctuating intra-thoracic pressure during respiration, and the passive relaxation of ventricle during diastole. The results of this simulation were consistent with the published case reports of exertional syncope in patients with AVS. The value of the EEC model is its ability to quantify the effect of a selective and gradable change in heart rate, ventricular contractility, or systemic vascular resistance on the hemodynamics during an exertional syncope in patients with severe AVS. PMID:23251225

Sever, Matjaž; Ribari?, Samo; Kordaš, Marjan

2012-01-01

272

Effects of ginsenosides-Rb1 on exercise-induced oxidative stress in forced swimming mice  

PubMed Central

Background: The fleshy root of Panax ginseng C.A. Meyer (ginseng) is one of the most well-known and valued herbs in traditional Chinese medicine. Ginsenosides are considered mainly responsible for the pharmacological activities of ginseng. The purpose of this study was to investigate the effects of ginsenoside-Rb1 (G-Rb1) on swimming exercise-induced oxidative stress in male mice. Materials and Methods: A total of 48 animals were randomly divided into four groups, with twelve mice in each group. The first, second and third groups were designed as G-Rb1 treatment groups, got 25, 50 and 100 mg/kg bodyweight of G-Rb1, respectively. The fourth group was designed as the control group, got physiologic saline. The mice were intragastrically administered once daily for 4 weeks. The weight-loaded forced swimming test was conducted on the final day of experimentation. Then the exhaustive swimming time, blood lactate, serum creatine kinase (CK), malondialdehyde (MDA) and antioxidant enzymes in liver of mice were measured. Results: The results showed that G-Rb1 could prolong the exhaustive swimming time and improve exercise endurance capacity of mice, as well as accelerate the clearance of blood lactate and decrease serum CK activities. Meanwhile, G-Rb1 could decrease MDA contents and increase superoxide dismutase, catalase, glutathione peroxidase activities in liver of mice. Conclusions: The study suggested that G-Rb1 possessed protective effects on swimming exercise-induced oxidative stress in mice. PMID:25422546

Qi, Bo; Zhang, Lan; Zhang, Zhiqun; Ouyang, Jiangqiong; Huang, Hui

2014-01-01

273

Proposed new mechanism for food and exercise induced anaphylaxis based on case studies  

PubMed Central

We present two cases of food and exercise-induced anaphylaxis (FEIA) in patients with a diagnosis of oral allergy syndrome (OAS) to the implicated foods. Patient A had FEIA attributed to fresh coriander and tomato and Patient B to fresh celery. These food allergens have been implicated in OAS and have structural antigenic similarity to that of birch and/or grass. Both patients’ allergies were confirmed by fresh skin prick tests. In both cases, strenuous exercise was antecedent to the systemic anaphylaxis reaction and subsequent ingestion without exercise produced only local symptoms of perioral pruritus. We review the current proposed mechanisms for food and exercise induced anaphylaxis to oral allergens and propose a novel and more biologically plausible mechanism. We hypothesize that the inhibitory effects of exercise on gastric acid secretion decreases the digestion of oral allergens and preserves structural integrity, thereby allowing continued systemic absorption of the allergen whether it be profilins, lipid transfer proteins, or other antigenic determinants. PMID:23509907

2013-01-01

274

Exercise-Induced Norepinephrine Decreases Circulating Hematopoietic Stem and Progenitor Cell Colony-Forming Capacity  

PubMed Central

A recent study showed that ergometry increased circulating hematopoietic stem and progenitor cell (CPC) numbers, but reduced hematopoietic colony forming capacity/functionality under normoxia and normobaric hypoxia. Herein we investigated whether an exercise-induced elevated plasma free/bound norepinephrine (NE) concentration could be responsible for directly influencing CPC functionality. Venous blood was taken from ten healthy male subjects (25.3+/?4.4 yrs) before and 4 times after ergometry under normoxia and normobaric hypoxia (FiO2<0.15). The circulating hematopoietic stem and progenitor cell numbers were correlated with free/bound NE, free/bound epinephrine (EPI), cortisol (Co) and interleukin-6 (IL-6). Additionally, the influence of exercise-induced NE and blood lactate (La) on CPC functionality was analyzed in a randomly selected group of subjects (n?=?6) in vitro under normoxia by secondary colony-forming unit granulocyte macrophage assays. Concentrations of free NE, EPI, Co and IL-6 were significantly increased post-exercise under normoxia/hypoxia. Ergometry-induced free NE concentrations found in vivo showed a significant impairment of CPC functionality in vitro under normoxia. Thus, ergometry-induced free NE was thought to trigger CPC mobilization 10 minutes post-exercise, but as previously shown impairs CPC proliferative capacity/functionality at the same time. The obtained results suggest that an ergometry-induced free NE concentration has a direct negative effect on CPC functionality. Cortisol may further influence CPC dynamics and functionality. PMID:25180783

Mangge, Harald; Pekovits, Karin; Fuchs, Robert; Allard, Nathalie; Schinagl, Lukas; Hofmann, Peter; Dohr, Gottfried; Wallner-Liebmann, Sandra; Domej, Wolfgang; Müller, Wolfram

2014-01-01

275

Skin testing with food, codeine, and histamine in exercise-induced anaphylaxis.  

PubMed

A 33-year-old Chinese woman with exercise-induced anaphylaxis after ingesting Chinese seafood noodle soup, was studied for skin test reactivity to food, histamine, and codeine. Prick skin tests were negative for shrimp, wheat, and chicken soup base, but were positive at 5 to 6 mm (wheal diameter) to the whole broth after it had been combined with the other ingredients. No significant (> 3 mm) wheals were observed in eight controls who were simultaneously tested with the broth. To assess the role of exercise, three series of skin tests were performed with histamine, codeine, and whole broth before and after aerobic exercise on two occasions. Codeine elicited consistent increases in wheal size after exercise compared with pre-exercise skin tests. Histamine and whole broth wheal sizes did not increase significantly. Three control subjects also had codeine and histamine skin tests before and after exercise, No exercise-associated increases were noted for codeine. Potential insights into mast cell abnormalities in exercise-induced anaphylaxis may be gained by skin testing patterns with codeine and other mast cell degranulating agents. PMID:8507042

Lin, R Y; Barnard, M

1993-06-01

276

Peroxisome biogenesis in mammalian cells  

PubMed Central

To investigate peroxisome assembly and human peroxisome biogenesis disorders (PBDs) such as Zellweger syndrome, thirteen different complementation groups (CGs) of Chinese hamster ovary (CHO) cell mutants defective in peroxisome biogenesis have been isolated and established as a model research system. Successful gene-cloning studies by a forward genetic approach utilized a rapid functional complementation assay of CHO cell mutants led to isolation of human peroxin (PEX) genes. Search for pathogenic genes responsible for PBDs of all 14 CGs is now completed together with the homology search by screening the human expressed sequence tag database using yeast PEX genes. Peroxins are divided into three groups: (1) peroxins including Pex3p, Pex16p, and Pex19p, are responsible for peroxisome membrane biogenesis via classes I and II pathways; (2) peroxins that function in matrix protein import; (3) those such as three forms of Pex11p, Pex11p?, Pex11p?, and Pex11p?, are involved in peroxisome proliferation where DLP1, Mff, and Fis1 coordinately function. In membrane assembly, Pex19p forms complexes in the cytosol with newly synthesized PMPs including Pex16p and transports them to the receptor Pex3p, whereby peroxisomal membrane is formed (Class I pathway). Pex19p likewise forms a complex with newly made Pex3p and translocates it to the Pex3p receptor, Pex16p (Class II pathway). In matrix protein import, newly synthesized proteins harboring peroxisome targeting signal type 1 or 2 are recognized by Pex5p or Pex7p in the cytoplasm and are imported to peroxisomes via translocation machinery. In regard to peroxisome-cytoplasmic shuttling of Pex5p, Pex5p initially targets to an 800-kDa docking complex consisting of Pex14p and Pex13p and then translocates to a 500-kDa RING translocation complex. At the terminal step, Pex1p and Pex6p of the AAA family mediate the export of Pex5p, where Cys-ubiquitination of Pex5p is essential for the Pex5p exit. PMID:25177298

Fujiki, Yukio; Okumoto, Kanji; Mukai, Satoru; Honsho, Masanori; Tamura, Shigehiko

2014-01-01

277

Temperature- and exercise-induced gene expression and metabolic enzyme changes in skeletal muscle of adult zebrafish (Danio rerio)  

PubMed Central

Both exercise training and cold acclimatization induce muscle remodelling in vertebrates, producing a more aerobic phenotype. In ectothermic species exercise training and cold-acclimatization represent distinct stimuli. It is currently unclear if these stimuli act through a common mechanism or if different mechanisms lead to a common phenotype. The goal of this study was to survey responses that represent potential mechanisms responsible for contraction- and temperature-induced muscle remodelling, using an ectothermic vertebrate. Separate groups of adult zebrafish (Danio rerio) were either swim trained or cold acclimatized for 4 weeks. We found that the mitochondrial marker enzyme citrate synthase (CS) was increased by 1.5× in cold and by 1.3× with exercise (P < 0.05). Cytochrome c oxidase (COx) was increased by 1.2× following exercise training (P < 0.05) and 1.2× (P = 0.07) with cold acclimatization. However, only cold acclimatization increased ?-hydroxyacyl-CoA dehydrogenase (HOAD) compared to exercise-trained (by 1.3×) and pyruvate kinase (PK) relative to control zebrafish. We assessed the whole-animal performance outcomes of these treatments. Maximum absolute sustained swimming speed (Ucrit) was increased in the exercise trained group but not in the cold acclimatized group. Real-time PCR analysis indicated that increases in CS are primarily transcriptionally regulated with exercise but not with cold treatments. Both treatments showed increases in nuclear respiratory factor (NRF)-1 mRNA which was increased by 2.3× in cold-acclimatized and 4× in exercise-trained zebrafish above controls. In contrast, peroxisome proliferator-activated receptor (PPAR)-? mRNA levels were decreased in both experimental groups while PPAR-?1 declined in exercise training only. Moreover, PPAR-? coactivator (PGC)-1? mRNA was not changed by either treatment. In zebrafish, both temperature and exercise produce a more aerobic phenotype, but there are stimulus-dependent responses (i.e. HOAD and PK activities). While similar changes in NRF-1 mRNA suggest that common responses might underlie aerobic muscle remodelling there are distinct changes (i.e. CS and PPAR-?1 mRNA) that contribute to specific temperature- and exercise-induced phenotypes. PMID:16990399

McClelland, Grant B; Craig, Paul M; Dhekney, Kalindi; Dipardo, Shawn

2006-01-01

278

Plant Peroxisomes: Biogenesis and Function  

PubMed Central

Peroxisomes are eukaryotic organelles that are highly dynamic both in morphology and metabolism. Plant peroxisomes are involved in numerous processes, including primary and secondary metabolism, development, and responses to abiotic and biotic stresses. Considerable progress has been made in the identification of factors involved in peroxisomal biogenesis, revealing mechanisms that are both shared with and diverged from non-plant systems. Furthermore, recent advances have begun to reveal an unexpectedly large plant peroxisomal proteome and have increased our understanding of metabolic pathways in peroxisomes. Coordination of the biosynthesis, import, biochemical activity, and degradation of peroxisomal proteins allows for highly dynamic responses of peroxisomal metabolism to meet the needs of a plant. Knowledge gained from plant peroxisomal research will be instrumental to fully understanding the organelle’s dynamic behavior and defining peroxisomal metabolic networks, thus allowing the development of molecular strategies for rational engineering of plant metabolism, biomass production, stress tolerance, and pathogen defense. PMID:22669882

Hu, Jianping; Baker, Alison; Bartel, Bonnie; Linka, Nicole; Mullen, Robert T.; Reumann, Sigrun; Zolman, Bethany K.

2012-01-01

279

Developmental regulation of mitochondrial biogenesis in Trypanosoma brucei  

Microsoft Academic Search

The metabolism ofTrypanosoma brucei undergoes a significant change as the parasite differentiates from the mammalian bloodstream form to the form found in the tse-tse fly vector. Because the mitochondria of bloodstream form cells lack cytochromes and several key citric acid cycle enzymes, the metabolism of these cells is mostly limited to glycolysis. The reducing equivalents generated by this process are

Jeffrey W. Priest; Stephen L. Hajduk

1994-01-01

280

Calorie restriction induces mitochondrial biogenesis and bioenergetic efficiency  

Microsoft Academic Search

Age-related accumulation of cellular damage and death has been linked to oxidative stress. Calorie restriction (CR) is the most robust, nongenetic intervention that increases lifespan and reduces the rate of aging in a variety of species. Mechanisms responsible for the antiaging effects of CR remain uncertain, but reduction of oxidative stress within mitochondria remains a major focus of research. CR

G. Lopez-Lluch; N. Hunt; B. Jones; M. Zhu; H. Jamieson; S. Hilmer; M. V. Cascajo; J. Allard; D. K. Ingram; P. Navas; R. de Cabo

2006-01-01

281

Stimulated Rat Liver Mitochondrial Biogenesis after Partial Hepatectomy  

Microsoft Academic Search

In Older to elucidate the response of mitochondria to the increase in cellulai energy demand after hepatectomy, we have examined the effects of partial hepatectomy and hepatic artery ligation on the energy-trans ducing system of rat liver mitochondria. Specific content of DNA in the mitochondria increased on the first day after the hepatectomy and reached 150% of the original value.

Masato Nagino; Masashi Tanaka; Morimitsu Nishikimi; Yuji Nimura; Hitoshi Kubota; Michio Kanai; Takehito Kato; Takayuki Ozawa

282

Therapeutic prospects for mitochondrial disease  

PubMed Central

Until even only a few years ago, the idea that effective therapies for human mitochondrial disorders resulting from dysfunction of the respiratory chain/oxidative phosphorylation system (OxPhos) could be developed was unimaginable. The obstacles to treating diseases caused by mutations in either mitochondrial DNA (mtDNA) or nuclear DNA (nDNA), and which had the potential to affect nearly every organ system, seemed overwhelming. However, while clinically applicable therapies still remain largely in the future, the landscape has changed dramatically; we can now envision the possibility of treating some of these disorders. Among these are techniques to upregulate mitochondrial biogenesis, to enhance organellar fusion and fission, to “shift heteroplasmy,” and to eliminate the burden of mutant mtDNAs via cytoplasmic transfer. PMID:20556877

Schon, Eric A.; DiMauro, Salvatore; Hirano, Michio; Gilkerson, Robert W.

2010-01-01

283

Exercise induced hypercoagulability, increased von Willebrand factor and decreased thyroid hormone concentrations in sled dogs  

PubMed Central

Background Sled dogs performing endurance races have been reported to have a high incidence of gastric erosions or ulcerations and an increased risk of gastro intestinal bleeding leading to death in some cases. In addition, these dogs also become hypothyroid during training and exercise. Canine hypothyroidism has been shown to correlate with decreased von Willebrand factor antigen and potentially increased bleeding tendency. Whether increased gastro intestinal bleeding risk is exacerbated due to changes in the hemostatic balance is unknown. The aim of this study was to investigate the hemostatic balance in sled dogs before and after exercise and in addition evaluate any correlation to thyroid status. Twenty sled dogs have been assessed in untrained and trained condition and immediately after exercise. The first sample was collected in the autumn following a resting period, and subsequently the dogs were exposed to increased intensity of training. After four months the peak of physical condition was reached and a 68 km long sled pulling exercise was performed. Samples were collected before and immediately after the exercise. Evaluated parameters were: plasma thromboelastographic (TEG) R, SP, ? and MA, activated partial thromboplastin time (aPTT), prothrombin time (PT), fibrinogen, von Willebrand factor (vWf), D-dimer, platelet number, thyroid hormones, hematocrit and C-reactive protein (CRP). Results Exercise induced an overall hypercoagulable state characterized by significant decreases of TEG R and SP and an increase of ?, increased concentrations of plasma vWf and decreased aPTT. In addition, a proinflammatory status was seen by a significant increase of serum CRP concentrations. Thyroid status was confirmed to be hypothyroid as training and exercise induced significant decrease of thyroxin (T4), free thyroxin (fT4) and thyroxin stimulating hormone (TSH) concentrations. Fibrinogen decreased significantly and PT increased. The training-induced changes showed correlation between T4, fT4 and aPTT and correlation between TSH and fibrinogen. Exercise-induced changes showed correlation between T4 and PT. Conclusions Exercise was associated with a hypercoagulable state and an increase of vWf concentration in this group of sled dogs. Decreased thyroid hormone concentrations after training and exercise were confirmed, but were associated with increased and not decreased vWf in this group of sled dogs. PMID:24507241

2014-01-01

284

Biogenesis of cytosolic ribosomes requires the essential iron–sulphur protein Rli1p and mitochondria  

PubMed Central

Mitochondria perform a central function in the biogenesis of cellular iron–sulphur (Fe/S) proteins. It is unknown to date why this biosynthetic pathway is indispensable for life, the more so as no essential mitochondrial Fe/S proteins are known. Here, we show that the soluble ATP-binding cassette (ABC) protein Rli1p carries N-terminal Fe/S clusters that require the mitochondrial and cytosolic Fe/S protein biogenesis machineries for assembly. Mutations in critical cysteine residues of Rli1p abolish association with Fe/S clusters and lead to loss of cell viability. Hence, the essential character of Fe/S clusters in Rli1p explains the indispensable character of mitochondria in eukaryotes. We further report that Rli1p is associated with ribosomes and with Hcr1p, a protein involved in rRNA processing and translation initiation. Depletion of Rli1p causes a nuclear export defect of the small and large ribosomal subunits and subsequently a translational arrest. Thus, ribosome biogenesis and function are intimately linked to the crucial role of mitochondria in the maturation of the essential Fe/S protein Rli1p. PMID:15660134

Kispal, Gyula; Sipos, Katalin; Lange, Heike; Fekete, Zsuzsanna; Bedekovics, Tibor; Janáky, Tamás; Bassler, Jochen; Aguilar Netz, Daili J; Balk, Janneke; Rotte, Carmen; Lill, Roland

2005-01-01

285

Redox regulation of mitochondrial fission, protein misfolding, synaptic damage, and neuronal cell death: potential implications for Alzheimer’s and Parkinson’s diseases  

Microsoft Academic Search

Normal mitochondrial dynamics consist of fission and fusion events giving rise to new mitochondria, a process termed mitochondrial\\u000a biogenesis. However, several neurodegenerative disorders manifest aberrant mitochondrial dynamics, resulting in morphological\\u000a abnormalities often associated with deficits in mitochondrial mobility and cell bioenergetics. Rarely, dysfunctional mitochondrial\\u000a occur in a familial pattern due to genetic mutations, but much more commonly patients manifest sporadic

Tomohiro Nakamura; Stuart A. Lipton

2010-01-01

286

Understanding the Functional Interplay between Mammalian Mitochondrial Hsp70 Chaperone Machine Components*S  

E-print Network

Understanding the Functional Interplay between Mammalian Mitochondrial Hsp70 Chaperone Machine 560012, Karnataka, India Mitochondria biogenesis requires the import of several precursor proteins that are synthesized in the cytosol. The mitochondrial heat shock protein 70 (mtHsp70) machinery components are highly

D' Silva, Patrick

287

Many different physiological and environmental stimuli induce mitochondrial proliferation in vertebrate muscles (see  

E-print Network

to a seasonal cold acclimation regime to assess the impact of erythrocyte age on skeletal muscle remodeling-induced mitochondrial proliferation in skeletal muscle, suggesting erythrocyte age was not an important influence in vertebrate muscles (see Hood, 2001; Moyes and Hood, 2003). Regulation of mitochondrial biogenesis may

McClelland, Grant B.

288

Mitochondrial donation Mitochondrial donation  

E-print Network

. Mitochondrial DNA does not affect the features that make each person unique, such as appearance and personality DNA disease, and multiple different organs can be affected as mitochondria are present in all tissues in 6500 children is thought to develop a serious mitochondrial disorder. There is no cure and our current

Newcastle upon Tyne, University of

289

The Mitochondrial Aminoacyl tRNA Synthetases: Genes and Syndromes  

PubMed Central

Mitochondrial respiratory chain (RC) disorders are a group of genetically and clinically heterogeneous diseases. This is because protein components of the RC are encoded by both mitochondrial and nuclear genomes and are essential in all cells. In addition, the biogenesis and maintenance of mitochondria, including mitochondrial DNA (mtDNA) replication, transcription, and translation, require nuclear-encoded genes. In the past decade, a growing number of syndromes associated with dysfunction of mtDNA translation have been reported. This paper reviews the current knowledge of mutations affecting mitochondrial aminoacyl tRNAs synthetases and their role in the pathogenic mechanisms underlying the different clinical presentations. PMID:24639874

2014-01-01

290

Exercise-induced pulmonary hemorrhage in a nonathlete: case report and review of physiology.  

PubMed

The integrity of the pulmonary blood-gas barrier is vulnerable to intense exercise in elite athletes, similar to the phenomenon of exercise-induced pulmonary hemorrhage in thoroughbred racehorses. A 50-year-old previously healthy man presented with acute onset shortness of breath, dry cough, and hypoxemia after engaging in an extremely vigorous game of handball. CT scan of the chest showed diffuse patchy air-space disease. Bronchoalveolar lavage revealed diffuse alveolar hemorrhage. Infectious etiologies and bleeding diatheses were excluded by laboratory testing. Serological tests for ANCA-associated vasculitis, lupus, and Goodpasture's disease also were negative. A transthoracic echocardiogram was normal. The patient recovered completely on supportive therapy in less than 72 h. This case demonstrates strenuous exercise as a cause of diffuse alveolar hemorrhage in a previously healthy male with no apparent underlying cardiopulmonary disease. PMID:24532148

Diwakar, Amit; Schmidt, Gregory A

2014-04-01

291

Exercise-Induced Cognitive Plasticity, Implications for Mild Cognitive Impairment and Alzheimer’s Disease  

PubMed Central

Lifestyle factors such as intellectual stimulation, cognitive and social engagement, nutrition, and various types of exercise appear to reduce the risk for common age-associated disorders such as Alzheimer’s disease (AD) and vascular dementia. In fact, many studies have suggested that promoting physical activity can have a protective effect against cognitive deterioration later in life. Slowing or a deterioration of walking speed is associated with a poor performance in tests assessing psychomotor speed and verbal fluency in elderly individuals. Fitness training influences a wide range of cognitive processes, and the largest positive impact observed is for executive (a.k.a. frontal lobe) functions. Studies show that exercise improves additional cognitive functions such as tasks mediated by the hippocampus, and result in major changes in plasticity in the hippocampus. Interestingly, this exercise-induced plasticity is also pronounced in APOE ?4 carriers who express a risk factor for late-onset AD that may modulate the effect of treatments. Based on AD staging by Braak and Braak (1991) and Braak et al. (1993) we propose that the effects of exercise occur in two temporo-spatial continua of events. The “inward” continuum from isocortex (neocortex) to entorhinal cortex/hippocampus for amyloidosis and a reciprocal “outward” continuum for neurofibrillary alterations. The exercise-induced hypertrophy of the hippocampus at the core of these continua is evaluated in terms of potential for prevention to stave off neuronal degeneration. Exercise-induced production of growth factors such as the brain-derived neurotrophic factor (BDNF) has been shown to enhance neurogenesis and to play a key role in positive cognitive effects. Insulin-like growth factor (IGF-1) may mediate the exercise-induced response to exercise on BDNF, neurogenesis, and cognitive performance. It is also postulated to regulate brain amyloid ? (A?) levels by increased clearance via the choroid plexus. Growth factors, specifically fibroblast growth factor and IGF-1 receptors and/or their downstream signaling pathways may interact with the Klotho gene which functions as an aging suppressor gene. Neurons may not be the only cells affected by exercise. Glia (astrocytes and microglia), neurovascular units and the Fourth Element may also be affected in a differential fashion by the AD process. Analyses of these factors, as suggested by the multi-dimensional matrix approach, are needed to improve our understanding of this complex multi-factorial process, which is increasingly relevant to conquering the escalating and intersecting world-wide epidemics of dementia, diabetes, and sarcopenia that threaten the global healthcare system. Physical activity and interventions aimed at enhancing and/or mimicking the effects of exercise are likely to play a significant role in mitigating these epidemics, together with the embryonic efforts to develop cognitive rehabilitation for neurodegenerative disorders. PMID:21602910

Foster, Philip P.; Rosenblatt, Kevin P.; Kuljiš, Rodrigo O.

2011-01-01

292

Increased renal tubular sodium reabsorption during exercise-induced hypervolemia in humans  

NASA Technical Reports Server (NTRS)

We tested the hypothesis that renal tubular Na(+) reabsorption increased during the first 24 h of exercise-induced plasma volume expansion. Renal function was assessed 1 day after no-exercise control (C) or intermittent cycle ergometer exercise (Ex, 85% of peak O(2) uptake) for 2 h before and 3 h after saline loading (12.5 ml/kg over 30 min) in seven subjects. Ex reduced renal blood flow (p-aminohippurate clearance) compared with C (0.83 +/- 0.12 vs. 1.49 +/- 0.24 l/min, P < 0.05) but did not influence glomerular filtration rates (97 +/- 10 ml/min, inulin clearance). Fractional tubular reabsorption of Na(+) in the proximal tubules was higher in Ex than in C (P < 0.05). Saline loading decreased fractional tubular reabsorption of Na(+) from 99.1 +/- 0.1 to 98.7 +/- 0.1% (P < 0.05) in C but not in Ex (99.3 +/- 0.1 to 99.4 +/- 0.1%). Saline loading reduced plasma renin activity and plasma arginine vasopressin levels in C and Ex, although the magnitude of decrease was greater in C (P < 0.05). These results indicate that, during the acute phase of exercise-induced plasma volume expansion, increased tubular Na(+) reabsorption is directed primarily to the proximal tubules and is associated with a decrease in renal blood flow. In addition, saline infusion caused a smaller reduction in fluid-regulating hormones in Ex. The attenuated volume-regulatory response acts to preserve distal tubular Na(+) reabsorption during saline infusion 24 h after exercise.

Nagashima, K.; Wu, J.; Kavouras, S. A.; Mack, G. W.

2001-01-01

293

Exercise induces interleukin-8 receptor (CXCR2) expression in human skeletal muscle.  

PubMed

Exercise induces a marked increase in interleukin-8 (IL-8) mRNA and protein expression within skeletal muscle fibres. Interleukin-8 belongs to a subfamily of CXC chemokines containing a Glu-Leu-Arg (ELR) motif. CXC chemokines with ELR motifs are potent angiogenic factors in vivo, and IL-8 has been shown to act as an angiogenic factor in human microvascular endothelial cells by binding to the CXC receptor 2 (CXCR2). In the present study, we examined the expression of the interleukin-8 receptor CXCR2 in human skeletal muscle biopsies after concentric exercise. Healthy volunteers were randomized to either 3 h of cycle ergometer exercise at 60% of maximum oxygen uptake (n = 8) or rest (n = 7). Muscle biopsy samples were obtained from the vastus lateralis before exercise (0 h), immediately after exercise (3 h), and at 4.5, 6, 9 and 24 h. Skeletal muscle CXCR2 mRNA increased significantly in response to exercise (3 and 4.5 h) when compared with pre-exercise samples. Expression of the CXCR2 protein was low in skeletal muscle biopsies before exercise and at the end of the exercise period (3 h). However, at 4.5-9 h, an increase in CXCR2 protein was seen in the vascular endothelium, and also slightly within the muscle fibres, as determined by immunohistochemistry. The present study demonstrates that concentric exercise induces CXCR2 mRNA and protein expression in the vascular endothelial cells of the muscle fibres. These findings suggest that muscle-derived IL-8 may act locally to stimulate angiogenesis through CXCR2 receptor signalling. PMID:17030560

Frydelund-Larsen, Lone; Penkowa, Milena; Akerstrom, Thorbjorn; Zankari, Alaa; Nielsen, Søren; Pedersen, Bente Klarlund

2007-01-01

294

Acute Exercise-Induced Response of Monocyte Subtypes in Chronic Heart and Renal Failure  

PubMed Central

Purpose. Monocytes (Mon1-2-3) play a substantial role in low-grade inflammation associated with high cardiovascular morbidity and mortality of patients with chronic kidney disease (CKD) and chronic heart failure (CHF). The effect of an acute exercise bout on monocyte subsets in the setting of systemic inflammation is currently unknown. This study aims (1) to evaluate baseline distribution of monocyte subsets in CHF and CKD versus healthy subjects (HS) and (2) to evaluate the effect of an acute exercise bout. Exercise-induced IL-6 and MCP-1 release are related to the Mon1-2-3 response. Methods. Twenty CHF patients, 20 CKD patients, and 15 HS were included. Before and after a maximal cardiopulmonary exercise test, monocyte subsets were quantified by flow cytometry: CD14++CD16?CCR2+ (Mon1), CD14++CD16+CCR2+ (Mon2), and CD14+CD16++CCR2? (Mon3). Serum levels of IL-6 and MCP-1 were determined by ELISA. Results. Baseline distribution of Mon1-2-3 was comparable between the 3 groups. Following acute exercise, %Mon2 and %Mon3 increased significantly at the expense of a decrease in %Mon1 in HS and in CKD. This response was significantly attenuated in CHF (P < 0.05). In HS only, MCP-1 levels increased following exercise; IL-6 levels were unchanged. Circulatory power was a strong and independent predictor of the changes in Mon1 (? = ?0.461, P < 0.001) and Mon3 (? = 0.449, P < 0.001); and baseline LVEF of the change in Mon2 (? = 0.441, P < 0.001). Conclusion. The response of monocytes to acute exercise is characterized by an increase in proangiogenic and proinflammatory Mon2 and Mon3 at the expense of phagocytic Mon1. This exercise-induced monocyte subset response is mainly driven by hemodynamic changes and not by preexistent low-grade inflammation. PMID:25587208

Van Craenenbroeck, Amaryllis H.; Hoymans, Vicky Y.; Verpooten, Gert A.; Vrints, Christiaan J.; Couttenye, Marie M.; Van Craenenbroeck, Emeline M.

2014-01-01

295

Effects of oral glutamine supplementation on exercise-induced gastrointestinal permeability and tight junction protein expression  

PubMed Central

The objectives of this study are threefold: 1) to assess whether 7 days of oral glutamine (GLN) supplementation reduces exercise-induced intestinal permeability; 2) whether supplementation prevents the proinflammatory response; and 3) whether these changes are associated with upregulation of the heat shock response. On separate occasions, eight human subjects participated in baseline testing and in GLN and placebo (PLA) supplementation trials, followed by a 60-min treadmill run. Intestinal permeability was higher in the PLA trial compared with baseline and GLN trials (0.0604 ± 0.047 vs. 0.0218 ± 0.008 and 0.0272 ± 0.007, respectively; P < 0.05). I?B? expression in peripheral blood mononuclear cells was higher 240 min after exercise in the GLN trial compared with the PLA trial (1.411 ± 0.523 vs. 0.9839 ± 0.343, respectively; P < 0.05). In vitro using the intestinal epithelial cell line Caco-2, we measured effects of GLN supplementation (0, 4, and 6 mM) on heat-induced (37° or 41.8°C) heat shock protein 70 (HSP70), heat shock factor-1 (HSF-1), and occludin expression. HSF-1 and HSP70 levels increased in 6 mM supplementation at 41°C compared with 0 mM at 41°C (1.785 ± 0.495 vs. 0.6681 ± 0.290, and 1.973 ± 0.325 vs. 1.133 ± 0.129, respectively; P < 0.05). Occludin levels increased after 4 mM supplementation at 41°C and 6 mM at 41°C compared with 0 mM at 41°C (1.236 ± 0.219 and 1.849 ± 0.564 vs. 0.7434 ± 0.027, respectively; P < 0.001). GLN supplementation prevented exercise-induced permeability, possibly through HSF-1 activation. PMID:24285149

Lanphere, Kathryn R.; Kravitz, Len; Mermier, Christine M.; Schneider, Suzanne; Dokladny, Karol; Moseley, Pope L.

2013-01-01

296

Level of dietary protein does not impact whole body protein turnover during an exercise induced energy deficit  

Technology Transfer Automated Retrieval System (TEKTRAN)

Introduction: This study examined the effect of a high protein diet on whole body protein turnover during an exercise-induced energy deficit. A sustained energy deficit induced by energy intake restriction increases protein catabolism which can cause lean-body mass loss. A high-protein diet has be...

297

A Systematic Review of the Literature on Screening for Exercise-Induced Asthma: Considerations for School Nurses  

ERIC Educational Resources Information Center

Asthma is a major cause of illness, missed school days, and hospitalization in children. One type of asthma common in children is exercise-induced asthma (EIA). EIA causes airway narrowing with symptoms of cough and shortness of breath during exercise. The purpose of this article is to review the literature relevant to screening children and…

Worrell, Kelly; Shaw, Michele R.; Postma, Julie; Katz, Janet R.

2015-01-01

298

Hematologic and hemorheological determinants of resting and exercise-induced hemoglobin oxygen desaturation in children with sickle cell disease.  

PubMed

The aim of the study was to determine the factors associated with resting and exercise-induced hemoglobin oxygen desaturation. The well-established six-minute walk test was conducted in 107 sickle cell children (50 with sickle hemoglobin C disease and 57 with sickle cell anemia) at steady state. Hemoglobin oxygen saturation was measured before and immediately after the six-minute walk test. Blood samples were obtained on the same day to measure hematologic and hemorheological parameters. Exercise-induced hemoglobin oxygen desaturation was defined as a drop in hemoglobin oxygen saturation of 3% or more at the end of the six-minute walk test compared to resting levels. No children with sickle hemoglobin C disease, but approximately 50% of children with sickle cell anemia showed mild or moderate oxygen desaturation at rest, which was independently associated with the percentage of reticulocytes. Exercise-induced hemoglobin oxygen desaturation was observed in 18% of children with sickle hemoglobin C disease and 34% of children with sickle cell anemia, and was independently associated with the six-minute walk test, acute chest syndrome rate and the strength of red blood cell aggregates in children with sickle cell anemia. No association was found in children with sickle hemoglobin C disease between exercise-induced hemoglobin oxygen desaturation and the measured parameters. Hemoglobin oxygen desaturation at rest was common in children with sickle cell anemia but not in children with sickle hemoglobin C disease, and was mainly associated with greater hemolysis. Physiological strain during exercise and red blood cell aggregation properties may predict the occurrence of exercise-induced hemoglobin oxygen desaturation in children with sickle cell anemia. PMID:23539539

Waltz, Xavier; Romana, Marc; Lalanne-Mistrih, Marie-Laure; Machado, Roberto F; Lamarre, Yann; Tarer, Vanessa; Hardy-Dessources, Marie-Dominique; Tressières, Benoît; Divialle-Doumdo, Lydia; Petras, Marie; Maillard, Frederic; Etienne-Julan, Maryse; Connes, Philippe

2013-07-01

299

HDL Biogenesis, Remodeling, and Catabolism.  

PubMed

In this chapter, we review how HDL is generated, remodeled, and catabolized in plasma. We describe key features of the proteins that participate in these processes, emphasizing how mutations in apolipoprotein A-I (apoA-I) and the other proteins affect HDL metabolism.The biogenesis of HDL initially requires functional interaction of apoA-I with the ATP-binding cassette transporter A1 (ABCA1) and subsequently interactions of the lipidated apoA-I forms with lecithin/cholesterol acyltransferase (LCAT). Mutations in these proteins either prevent or impair the formation and possibly the functionality of HDL.Remodeling and catabolism of HDL is the result of interactions of HDL with cell receptors and other membrane and plasma proteins including hepatic lipase (HL), endothelial lipase (EL), phospholipid transfer protein (PLTP), cholesteryl ester transfer protein (CETP), apolipoprotein M (apoM), scavenger receptor class B type I (SR-BI), ATP-binding cassette transporter G1 (ABCG1), the F1 subunit of ATPase (Ecto F1-ATPase), and the cubulin/megalin receptor.Similarly to apoA-I, apolipoprotein E and apolipoprotein A-IV were shown to form discrete HDL particles containing these apolipoproteins which may have important but still unexplored functions. Furthermore, several plasma proteins were found associated with HDL and may modulate its biological functions. The effect of these proteins on the functionality of HDL is the topic of ongoing research. PMID:25522986

Zannis, Vassilis I; Fotakis, Panagiotis; Koukos, Georgios; Kardassis, Dimitris; Ehnholm, Christian; Jauhiainen, Matti; Chroni, Angeliki

2015-01-01

300

Mitochondrial Myopathies  

MedlinePLUS

... include: • Kearns-Sayre syndrome (KSS) • Leigh syndrome • mitochondrial DNA depletion syndrome (MDS) • mitochondrial encephalomyopathy, lactic acidosis and ... on swallowing, speech and eye movements. MDS: mitochondrial DNA depletion syndrome Inheritance pattern: Mendelian Onset: infancy Features: ...

301

Opposing roles of mitochondrial and nuclear PARP1 in the regulation of mitochondrial and nuclear DNA integrity: implications for the regulation of mitochondrial function.  

PubMed

The positive role of PARP1 in regulation of various nuclear DNA transactions is well established. Although a mitochondrial localization of PARP1 has been suggested, its role in the maintenance of the mitochondrial DNA is currently unknown. Here we investigated the role of PARP1 in the repair of the mitochondrial DNA in the baseline and oxidative stress conditions. We used wild-type A549 cells or cells depleted of PARP1. Our data show that intra-mitochondrial PARP1 interacts with a key mitochondrial-specific DNA base excision repair (BER) enzymes, namely EXOG and DNA polymerase gamma (Pol?), which under oxidative stress become poly(ADP-ribose)lated (PARylated). Interaction between mitochondrial BER enzymes was significantly affected in the presence of PARP1. Moreover, the repair of the oxidative-induced damage to the mitochondrial DNA in PARP1-depleted cells was found to be more robust compared to control counterpart. In addition, mitochondrial biogenesis was enhanced in PARP1-depleted cells, including mitochondrial DNA copy number and mitochondrial membrane potential. This observation was further confirmed by analysis of lung tissue isolated from WT and PARP1 KO mice. In summary, we conclude that mitochondrial PARP1, in opposite to nuclear PARP1, exerts a negative effect on several mitochondrial-specific transactions including the repair of the mitochondrial DNA. PMID:25378300

Szczesny, Bartosz; Brunyanszki, Attila; Olah, Gabor; Mitra, Sankar; Szabo, Csaba

2014-12-01

302

Evidence of a bigenomic regulation of mitochondrial gene expression by thyroid hormone during rat brain development  

SciTech Connect

Hypothyroidism during early mammalian brain development is associated with decreased expression of various mitochondrial encoded genes along with evidence for mitochondrial dysfunction. However, in-spite of the similarities between neurological disorders caused by perinatal hypothyroidism and those caused by various genetic mitochondrial defects we still do not know as to how thyroid hormone (TH) regulates mitochondrial transcription during development and whether this regulation by TH is nuclear mediated or through mitochondrial TH receptors? We here in rat cerebellum show that hypothyroidism causes reduction in expression of nuclear encoded genes controlling mitochondrial biogenesis like PGC-1{alpha}, NRF-1{alpha} and Tfam. Also, we for the first time demonstrate a mitochondrial localization of thyroid hormone receptor (mTR) isoform in developing brain capable of binding a TH response element (DR2) present in D-loop region of mitochondrial DNA. These results thus indicate an integrated nuclear-mitochondrial cross talk in regulation of mitochondrial transcription by TH during brain development.

Sinha, Rohit Anthony; Pathak, Amrita; Mohan, Vishwa; Babu, Satish; Pal, Amit; Khare, Drirh [Department of Endocrinology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014 (India)] [Department of Endocrinology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014 (India); Godbole, Madan M., E-mail: madangodbole@yahoo.co.in [Department of Endocrinology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014 (India)

2010-07-02

303

Caloric Restriction and the Nutrient-Sensing PGC-1? in Mitochondrial Homeostasis: New Perspectives in Neurodegeneration  

PubMed Central

Mitochondrial activity progressively declines during ageing and in many neurodegenerative diseases. Caloric restriction (CR) has been suggested as a dietary intervention that is able to postpone the detrimental aspects of aging as it ameliorates mitochondrial performance. This effect is partially due to increased mitochondrial biogenesis. The nutrient-sensing PGC-1? is a transcriptional coactivator that promotes the expression of mitochondrial genes and is induced by CR. It is believed that many of the mitochondrial and metabolic benefits of CR are due to increased PGC-1? activity. The increase of PGC-1? is also positively linked to neuroprotection and its decrement has been involved in the pathogenesis of many neurodegenerative diseases. This paper aims to summarize the current knowledge about the role of PGC-1? in neuronal homeostasis and the beneficial effects of CR on mitochondrial biogenesis and function. We also discuss how PGC-1?-governed pathways could be used as target for nutritional intervention to prevent neurodegeneration. PMID:22829833

Lettieri Barbato, Daniele; Baldelli, Sara; Pagliei, Beatrice; Aquilano, Katia; Ciriolo, Maria Rosa

2012-01-01

304

Hemodynamic effects of the calcium channel blocker pranidipine on exercise-induced angina.  

PubMed

Hemodynamic effects of a newly developed calcium channel blocker, pranidipine, on dynamic exercise-induced angina were investigated. Ten patients with stable effort angina pectoris underwent symptom-limited bicycle ergometer exercise testings before and after a single oral administration of pranidipine, and effects of pranidipine on systemic, cardiac and coronary hemo-dynamics induced by dynamic exercise were evaluated invasively. Pranidipine administration reduced systemic vascular resistance (from 1,764 +/- 109 to 1,115 +/- 60 dynes.sec/cm5; p < 0.01 at test, and from 1,120 +/- 102 to 795 +/- 62 dynes.sec/cm5; p < 0.05 at peak exercise) and mean arterial pressure (from 93 +/- 5 to 76 +/- 3 mmHg; p < 0.01 at test, and from 85 +/- 7 to 72 +/- 6 mmHg; p < 0.05 at peak exercise) with the increase in heart rate and cardiac index throughout exercise. Pranidipine also decreased coronary vascular resistance from 1.29 +/- 0.21 to 0.89 +/- 0.17 mmHg/ml/min (p < 0.05) at resting condition. At peak exercise, rate-pressure product and myocardial oxygen consumption decreased (from 237 +/- 21 to 215 +/- 18 x 10(2); p < 0.05, and from 31.3 +/- 7.5 to 21.7 +/- 3.9 ml/min; p < 0.05, respectively), while coronary vascular resistance did not change significantly. Furthermore, pranidipine mitigated ST-segment depression and elevation of pulmonary artery wedge pressure at peak exercise (from 0.20 +/- 0.03 to 0.13 +/- 0.02 mV; p < 0.01, and from 25 +/- 3 to 11 +/- 2 mmHg; p < 0.01, respectively). These results suggest that the major therapeutic effects of pranidipine for dynamic exercise-induced angina would be to reduce myocardial oxygen demand by improving peripheral circulation and reducing preload and afterload.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7834162

Nishinaka, Y; Yokota, M; Watanabe, M; Sobue, T; Iwase, M; Ukai, M; Ando, A; Nagata, K; Saito, H

1994-10-01

305

The life of plant mitochondrial complex I.  

PubMed

The mitochondrial NADH dehydrogenase complex (complex I) of the respiratory chain has several remarkable features in plants: (i) particularly many of its subunits are encoded by the mitochondrial genome, (ii) its mitochondrial transcripts undergo extensive maturation processes (e.g. RNA editing, trans-splicing), (iii) its assembly follows unique routes, (iv) it includes an additional functional domain which contains carbonic anhydrases and (v) it is, indirectly, involved in photosynthesis. Comprising about 50 distinct protein subunits, complex I of plants is very large. However, an even larger number of proteins are required to synthesize these subunits and assemble the enzyme complex. This review aims to follow the complete "life cycle" of plant complex I from various molecular perspectives. We provide arguments that complex I represents an ideal model system for studying the interplay of respiration and photosynthesis, the cooperation of mitochondria and the nucleus during organelle biogenesis and the evolution of the mitochondrial oxidative phosphorylation system. PMID:24561573

Braun, Hans-Peter; Binder, Stefan; Brennicke, Axel; Eubel, Holger; Fernie, Alisdair R; Finkemeier, Iris; Klodmann, Jennifer; König, Ann-Christine; Kühn, Kristina; Meyer, Etienne; Obata, Toshihiro; Schwarzländer, Markus; Takenaka, Mizuki; Zehrmann, Anja

2014-11-01

306

PGC-1? is coupled to HIF-1?-dependent gene expression by increasing mitochondrial oxygen consumption in skeletal muscle cells  

PubMed Central

Mitochondrial biogenesis occurs in response to increased cellular ATP demand. The mitochondrial electron transport chain requires molecular oxygen to produce ATP. Thus, increased ATP generation after mitochondrial biogenesis results in increased oxygen demand that must be matched by a corresponding increase in oxygen supply. We found that overexpression of peroxisome proliferator-activated receptor-? coactivator 1? (PGC-1?), which increases mitochondrial biogenesis in primary skeletal muscle cells, leads to increased expression of a cohort of genes known to be regulated by the dimeric hypoxia-inducible factor (HIF), a master regulator of the adaptive response to hypoxia. PGC-1?-dependent induction of HIF target genes under physiologic oxygen concentrations is not through transcriptional coactivation of HIF or up-regulation of HIF-1? mRNA but through HIF-1? protein stabilization. It occurs because of intracellular hypoxia as a result of increased oxygen consumption after mitochondrial biogenesis. Thus, we propose that at physiologic oxygen concentrations, PGC-1? is coupled to HIF signaling through the regulation of intracellular oxygen availability, allowing cells and tissues to match increased oxygen demand after mitochondrial biogenesis with increased oxygen supply. PMID:19179292

O'Hagan, Kathleen A.; Cocchiglia, Sinead; Zhdanov, Alexander V.; Tambuwala, Murtaza M.; Cummins, Eoin P.; Monfared, Mona; Agbor, Terence A.; Garvey, John F.; Papkovsky, Dmitri B.; Taylor, Cormac T.; Allan, Bernard B.

2009-01-01

307

Assessment of eccentric exercise-induced muscle damage of the elbow flexors by tensiomyography.  

PubMed

Exercise induced muscle damage (EIMD) impairs maximal torque production which can cause a decline in athletic performance and/or mobility. EIMD is commonly assessed by using maximal voluntary contraction (MVC), creatine kinase (CK) and muscle soreness. We propose as an additional technique, tensiomyography (TMG), recently introduced to measure mechanical and muscle contractile characteristics. The purpose of this study was to determine the validity of TMG in detecting changes in maximal torque following EIMD. Nineteen participants performed eccentric elbow flexions to achieve EIMD on the non- dominant arm and used the dominant elbow flexor as a control. TMG parameters, MVC and rate of torque development (RTD) were measured prior to EIMD and repeated for another six consecutive days. Creatine kinase, muscle soreness and limb girth were also measured during this period. Twenty four hours after inducing EIMD, MVC torque, RTD and TMG maximal displacement had significantly (p<0.01) declined by 37%, 44% and 31%, respectively. By day 6 MVC, RTD and TMG recovered to 12%, 24% and 17% of respective pre-EIMD values. In conclusion, as hypothesised TMG maximal displacement significantly followed other standard EIMD responses. This could therefore be useful in detecting muscle damage from impaired muscle function and its recovery following EIMD. PMID:22336641

Hunter, Angus M; Galloway, Stuart D R; Smith, Iain J; Tallent, Jamie; Ditroilo, Massimiliano; Fairweather, Malcolm M; Howatson, Glyn

2012-06-01

308

Contrast Water Therapy and Exercise Induced Muscle Damage: A Systematic Review and Meta-Analysis  

PubMed Central

The aim of this systematic review was to examine the effect of Contrast Water Therapy (CWT) on recovery following exercise induced muscle damage. Controlled trials were identified from computerized literature searching and citation tracking performed up to February 2013. Eighteen trials met the inclusion criteria; all had a high risk of bias. Pooled data from 13 studies showed that CWT resulted in significantly greater improvements in muscle soreness at the five follow-up time points (<6, 24, 48, 72 and 96 hours) in comparison to passive recovery. Pooled data also showed that CWT significantly reduced muscle strength loss at each follow-up time (<6, 24, 48, 72 and 96 hours) in comparison to passive recovery. Despite comparing CWT to a large number of other recovery interventions, including cold water immersion, warm water immersion, compression, active recovery and stretching, there was little evidence for a superior treatment intervention. The current evidence base shows that CWT is superior to using passive recovery or rest after exercise; the magnitudes of these effects may be most relevant to an elite sporting population. There seems to be little difference in recovery outcome between CWT and other popular recovery interventions. PMID:23626806

Bieuzen, François; Bleakley, Chris M.; Costello, Joseph Thomas

2013-01-01

309

Physical exercise-induced hippocampal neurogenesis and antidepressant effects are mediated by the adipocyte hormone adiponectin  

PubMed Central

Adiponectin (ADN) is an adipocyte-secreted protein with insulin-sensitizing, antidiabetic, antiinflammatory, and antiatherogenic properties. Evidence is also accumulating that ADN has neuroprotective activities, yet the underlying mechanism remains elusive. Here we show that ADN could pass through the blood–brain barrier, and elevating its levels in the brain increased cell proliferation and decreased depression-like behaviors. ADN deficiency did not reduce the basal hippocampal neurogenesis or neuronal differentiation but diminished the effectiveness of exercise in increasing hippocampal neurogenesis. Furthermore, exercise-induced reduction in depression-like behaviors was abrogated in ADN-deficient mice, and this impairment in ADN-deficient mice was accompanied by defective running-induced phosphorylation of AMP-activated protein kinase (AMPK) in the hippocampal tissue. In vitro analyses indicated that ADN itself could increase cell proliferation of both hippocampal progenitor cells and Neuro2a neuroblastoma cells. The neurogenic effects of ADN were mediated by the ADN receptor 1 (ADNR1), because siRNA targeting ADNR1, but not ADNR2, inhibited the capacity of ADN to enhance cell proliferation. These data suggest that adiponectin may play a significant role in mediating the effects of exercise on hippocampal neurogenesis and depression, possibly by activation of the ADNR1/AMPK signaling pathways, and also raise the possibility that adiponectin and its agonists may represent a promising therapeutic treatment for depression. PMID:25331877

Yau, Suk Yu; Li, Ang; Hoo, Ruby L. C.; Ching, Yick Pang; Christie, Brian R.; Lee, Tatia M. C.; Xu, Aimin; So, Kwok-Fai

2014-01-01

310

Physical exercise-induced hippocampal neurogenesis and antidepressant effects are mediated by the adipocyte hormone adiponectin.  

PubMed

Adiponectin (ADN) is an adipocyte-secreted protein with insulin-sensitizing, antidiabetic, antiinflammatory, and antiatherogenic properties. Evidence is also accumulating that ADN has neuroprotective activities, yet the underlying mechanism remains elusive. Here we show that ADN could pass through the blood-brain barrier, and elevating its levels in the brain increased cell proliferation and decreased depression-like behaviors. ADN deficiency did not reduce the basal hippocampal neurogenesis or neuronal differentiation but diminished the effectiveness of exercise in increasing hippocampal neurogenesis. Furthermore, exercise-induced reduction in depression-like behaviors was abrogated in ADN-deficient mice, and this impairment in ADN-deficient mice was accompanied by defective running-induced phosphorylation of AMP-activated protein kinase (AMPK) in the hippocampal tissue. In vitro analyses indicated that ADN itself could increase cell proliferation of both hippocampal progenitor cells and Neuro2a neuroblastoma cells. The neurogenic effects of ADN were mediated by the ADN receptor 1 (ADNR1), because siRNA targeting ADNR1, but not ADNR2, inhibited the capacity of ADN to enhance cell proliferation. These data suggest that adiponectin may play a significant role in mediating the effects of exercise on hippocampal neurogenesis and depression, possibly by activation of the ADNR1/AMPK signaling pathways, and also raise the possibility that adiponectin and its agonists may represent a promising therapeutic treatment for depression. PMID:25331877

Yau, Suk Yu; Li, Ang; Hoo, Ruby L C; Ching, Yick Pang; Christie, Brian R; Lee, Tatia M C; Xu, Aimin; So, Kwok-Fai

2014-11-01

311

Exercise-induced seizures and lateral asymmetry in patients with temporal lobe epilepsy???  

PubMed Central

Objective The objective of this case report is to better characterize the clinical features and potential pathophysiological mechanisms of exercise-induced seizures. Methods We report a case series of ten patients from a tertiary epilepsy center, where a clear history was obtained of physical exercise as a reproducible trigger for seizures. Results The precipitating type of exercise was quite specific for each patient, and various forms of exercise are described including running, swimming, playing netball, dancing, cycling, weight lifting, and martial arts. The level of physical exertion also correlated with the likelihood of seizure occurrence. All ten patients had temporal lobe abnormalities, with nine of the ten patients having isolated temporal lobe epilepsies, as supported by seizure semiology, EEG recordings, and both structural and functional imaging. Nine of the ten patients had seizures that were lateralized to the left (dominant) hemisphere. Five patients underwent surgical resection, with no successful long-term postoperative outcomes. Conclusions Exercise may be an underrecognized form of reflex epilepsy, which tended to be refractory to both medical and surgical interventions in our patients. Almost all patients in our cohort had seizures localizing to the left temporal lobe. We discuss potential mechanisms by which exercise may precipitate seizures, and its relevance regarding our understanding of temporal lobe epilepsy and lateralization of seizures. Recognition of, as well as advice regarding avoidance of, known triggers forms an important part of management of these patients.

Kamel, Jordan T.; Badawy, Radwa A.B.; Cook, Mark J.

2014-01-01

312

Exercise-induced stress resistance is independent of exercise controllability and the medial prefrontal cortex  

PubMed Central

Exercise increases resistance against stress-related disorders such as anxiety and depression. Similarly, the perception of control is a powerful predictor of neurochemical and behavioral responses to stress, but whether the experience of choosing to exercise, and exerting control over that exercise, is a critical factor in producing exercise-induced stress resistance is unknown. The current studies investigated whether the protective effects of exercise against the anxiety- and depression-like consequences of stress are dependent on exercise controllability and a brain region implicated in the protective effects of controllable experiences, the medial prefrontal cortex. Adult male Fischer 344 rats remained sedentary, were forced to run on treadmills or motorised running wheels, or had voluntary access to wheels for 6 weeks. Three weeks after exercise onset, rats received sham surgery or excitotoxic lesions of the medial prefrontal cortex. Rats were exposed to home cage or uncontrollable tail shock treatment three weeks later. Shock-elicited fear conditioning and shuttle box escape testing occurred the next day. Both forced and voluntary wheel running, but not treadmill training, prevented the exaggerated fear conditioning and interference with escape learning produced by uncontrollable stress. Lesions of the medial prefrontal cortex failed to eliminate the protective effects of forced or voluntary wheel running. These data suggest that exercise controllability and the medial prefrontal cortex are not critical factors in conferring the protective effects of exercise against the affective consequences of stressor exposure, and imply that exercise perceived as forced may still benefit affect and mental health. PMID:23121339

Greenwood, Benjamin N.; Spence, Katie G.; Crevling, Danielle M.; Clark, Peter J.; Craig, Wendy C.; Fleshner, Monika

2014-01-01

313

Exercise-Induced Changes in Iron Status and Hepcidin Response in Female Runners  

PubMed Central

Background and Aims Exercise-induced iron deficiency is a common finding in endurance athletes. It has been suggested recently that hepcidin may be an important mediator in this process. Objective To determine hepcidin levels and markers of iron status during long-term exercise training in female runners with depleted and normal iron stores. Methods Fourteen runners were divided into two groups according to iron status. Blood samples were taken during a period of eight weeks at baseline, after training and after ten days’ recovery phase. Results Of 14 runners, 7 were iron deficient at baseline and 10 after training. Hepcidin was lower at recovery compared with baseline (p<0.05). The mean cell haemoglobin content, haemoglobin content per reticulocyte and total iron binding capacity all decreased, whereas soluble transferrin receptor and hypochromic red cells increased after training and recovery (p<0.05 for all). Conclusion The prevalence of depleted iron stores was 71% at the end of the training phase. Hepcidin and iron stores decreased during long-term running training and did not recover after ten days, regardless of baseline iron status. PMID:23472137

Auersperger, Irena; Škof, Branko; Leskošek, Bojan; Knap, Bojan; Jerin, Aleš; Lainscak, Mitja

2013-01-01

314

Does exercise-induced muscle damage play a role in skeletal muscle hypertrophy?  

PubMed

Exercise-induced muscle damage (EIMD) occurs primarily from the performance of unaccustomed exercise, and its severity is modulated by the type, intensity, and duration of training. Although concentric and isometric actions contribute to EIMD, the greatest damage to muscle tissue is seen with eccentric exercise, where muscles are forcibly lengthened. Damage can be specific to just a few macromolecules of tissue or result in large tears in the sarcolemma, basal lamina, and supportive connective tissue, and inducing injury to contractile elements and the cytoskeleton. Although EIMD can have detrimental short-term effects on markers of performance and pain, it has been hypothesized that the associated skeletal muscle inflammation and increased protein turnover are necessary for long-term hypertrophic adaptations. A theoretical basis for this belief has been proposed, whereby the structural changes associated with EIMD influence gene expression, resulting in a strengthening of the tissue and thus protection of the muscle against further injury. Other researchers, however, have questioned this hypothesis, noting that hypertrophy can occur in the relative absence of muscle damage. Therefore, the purpose of this article will be twofold: (a) to extensively review the literature and attempt to determine what, if any, role EIMD plays in promoting skeletal muscle hypertrophy and (b) to make applicable recommendations for resistance training program design. PMID:22344059

Schoenfeld, Brad J

2012-05-01

315

Prostaglandin production contributes to exercise-induced vasodilation in heart failure.  

PubMed

Endothelial release of prostaglandins may contribute to exercise-induced skeletal muscle arteriolar vasodilation in patients with heart failure. To test this hypothesis, we examined the effect of indomethacin on leg circulation and metabolism in eight chronic heart failure patients, aged 55 +/- 4 yr. Central hemodynamics and leg blood flow, determined by thermodilution, and leg metabolic parameters were measured during maximum treadmill exercise before and 2 h after oral administration of indomethacin (75 mg). Leg release of 6-ketoprostaglandin F1alpha was also measured. During control exercise, leg blood flow increased from 0.34 +/- 0.03 to 1. 99 +/- 0.19 l/min (P < 0.001), leg O2 consumption from 13.6 +/- 1.8 to 164.5 +/- 16.2 ml/min (P < 0.001), and leg prostanoid release from 54.1 +/- 8.5 to 267.4 +/- 35.8 pg/min (P < 0.001). Indomethacin suppressed release of prostaglandin F1alpha (P < 0.001) throughout exercise and decreased leg blood flow during exercise (P < 0.05). This was associated with a corresponding decrease in leg O2 consumption (P < 0.05) and a higher level of femoral venous lactate at peak exercise (P < 0.01). These data suggest that release of vasodilatory prostaglandins contributes to skeletal muscle arteriolar vasodilation in patients with heart failure. PMID:9390965

Lang, C C; Chomsky, D B; Butler, J; Kapoor, S; Wilson, J R

1997-12-01

316

Exercise Effects on Erythrocyte Deformability in Exercise-induced Arterial Hypoxemia.  

PubMed

Exercise-induced arterial hypoxemia (EIAH) is often found in endurance-trained subjects at high exercise intensity. The role of erythrocyte deformability (ED) in EIAH has been scarcely explored. We aimed to explore the role of erythrocyte properties and lactate accumulation in the response of ED in EIAH. ED was determined in 10 sedentary and in 16 trained subjects, both before and after a maximal incremental test, and after recovery, along with mean corpuscular volume (MCV) and red blood cell lactate concentrations. EIAH was found in 6 trained subjects (?SaO2=-8.25±4.03%). Sedentary and non-EIAH trained subjects showed reduced ED after exercise, while no effect on ED was found in EIAH trained subjects. After exercise, lactate concentrations rose and MCV increased equally in all groups. ED is strongly driven by cell volume, but the different ED response to exercise in EIAH shows that other cellular mechanisms may be implicated. Interactions between membrane and cytoskeleton, which have been found to be O2-regulated, play a role in ED. The drop in SaO2 in EIAH subjects can improve ED response to exercise. This can be an adaptive mechanism that enhances muscular and pulmonary perfusion, and allows the achievement of high exercise intensity in EIAH despite lower O2 arterial transport. PMID:25429547

Alis, R; Sanchis-Gomar, F; Ferioli, D; Torre, A La; Blesa, J R; Romagnoli, M

2014-11-27

317

Coronary collaterals reduce the duration of exercise-induced ischemia by allowing a faster recovery.  

PubMed

The role of collaterals in influencing postischemic recovery after exercise testing has not been investigated previously. We studied 54 patients (mean age 59 +/- 6 years) with effort-induced angina and documented coronary disease who underwent exercise testing and thallium-201 myocardial scintigraphy. On angiography, 30 patients (group A) exhibited visible collaterals (grade 2 to 3, Cohen and Rentrop classification) perfusing the ischemic zone, whereas the other 24 (group B) did not. Patients with collaterals had more severe coronary artery disease (Gensini score 46.9 +/- 16 vs 28.6 +/- 18; p less than 0.001) and more severe impairment of coronary flow reserve (time and rate-pressure product to 1 mm ST segment depression 3.5 +/- 0.8 vs 4.8 +/- 0.6 minutes, p less than 0.01; 14,189 +/- 2451 vs 16,081 +/- 2215 beats/min x mm Hg, p less than 0.04, respectively). However, in these patients the ECG returned to baseline more rapidly after exercise (5.5 +/- 1.6 vs 11.7 +/- 3.3 minutes; p less than 0.001). Therefore, although collaterals do not apparently prevent or delay the development of exercise-induced ischemia, they can limit its duration by allowing a faster recovery. PMID:1615827

Bonetti, F; Margonato, A; Mailhac, A; Carandente, O; Cappelletti, A; Ballarotto, C; Chierchia, S L

1992-07-01

318

Cyc2p, a Membrane-bound Flavoprotein Involved in the Maturation of Mitochondrial c-Type Cytochromes*S  

E-print Network

Cyc2p, a Membrane-bound Flavoprotein Involved in the Maturation of Mitochondrial c-Type Cytochromes-Sud, Orsay 91405, France Mitochondrial apocytochrome c and c1 are converted to their holoforms­III) for the biogenesis of c-type cytochromes have evolved in bacteria, plastids, and mitochondria (for reviews, see Refs

Hamel, Patrice

319

A low dose of alcohol does not impact skeletal muscle performance after exercise-induced muscle damage  

Microsoft Academic Search

Moderate, acute alcohol consumption after eccentric exercise has been shown to magnify the muscular weakness that is typically\\u000a associated with exercise-induced muscle damage (EIMD). As it is not known whether this effect is dose-dependent, the aim of\\u000a this study was to investigate the effect of a low dose of alcohol on EIMD-related losses in muscular performance. Ten healthy\\u000a males performed

Matthew J. Barnes; Toby Mündel; Stephen R. Stannard

2011-01-01

320

Effects of eccentric exercise-induced muscle injury on blood levels of platelet activating factor (PAF) and other inflammatory markers  

Microsoft Academic Search

It has been reported that exercise with eccentric contractions can induce damage and inflammation in human muscle tissue,\\u000a the severity of which depends on the duration and the intensity of exercise. Platelet activating factor (PAF) is a potent\\u000a inflammatory mediator implicated in a series of pathophysiological conditions. We sought to investigate the relationship between\\u000a PAF and eccentric exercise induced muscle

George A. Milias; Tzortzis Nomikos; Elizabeth Fragopoulou; Spyridon Athanasopoulos; Smaragdi Antonopoulou

2005-01-01

321

Recording locations in multichannel magnetocardiography and body surface potential mapping sensitive for regional exercise-induced myocardial ischemia  

Microsoft Academic Search

Introduction This study aimed to identify the optimal locations in multichannel magnetocardiography (MCG) and body surface potential mapping\\u000a (BSPM) to detect exercise-induced myocardial ischemia. Methods We studied 17 healthy controls and 24 coronary artery disease (CAD) patients with stenosis in one of the main coronary artery\\u000a branches: left anterior descending (LAD) in 11 patients, right (RCA) in 7 patients, and

Helena Hänninen; Panu Takala; Markku Mäkijärvi; Juha Montonen; Petri Korhonen; Lasse Oikarinen; Kim Simelius; Jukka Nenonen; Toivo Katila; Lauri Toivonen

2001-01-01

322

The effects of nitroglycerin on exercise-induced regional myocardial contractile dysfunction are not diminished by pretreatment with dihydroergotamine.  

PubMed Central

1 Because controversy exists regarding the effects of dihydroergotamine (DHE) on the performance of underperfused myocardium, the effects of DHE were investigated in a model of exercise-induced regional myocardial dysfunction in conscious dogs. 2 We also investigated a possible functional antagonism between DHE and nitroglycerin that might reduce the latter drug's antianginal efficacy. 3 Investigations were carried out in conscious dogs. After stenosis of the circumflex branch of the left coronary artery that minimally affected resting myocardial function, treadmill exercise induced transient regional contractile dysfunction. Heart rate, arterial blood pressure, left ventricular dp/dtmax and left ventricular end-diastolic pressure were registered. Regional contractile performance was assessed by ultrasonic distance measurement in the underperfused and in a normally perfused area. 4 DHE (5 micrograms kg-1, i.v.) induced a decrease in left ventricular dp/dtmax at rest and during exercise. DHE did not cause a deterioration in contractile function in the ischaemic myocardium, but led to a slight although not significant improvement in regional myocardial function. 5 After pretreatment with DHE, infusion of nitroglycerin (15 micrograms kg-1, i.v.) induced an improvement in the underperfused myocardial area during treadmill exercise, accompanied by a decrease in diastolic arterial pressure and left ventricular end-diastolic pressure and an increase in left ventricular dp/dtmax. 6 These results suggest that DHE will not worsen exercise-induced angina pectoris, and that the antianginal efficacy of nitroglycerin will not be neutralized by pretreatment with DHE. PMID:3117154

Schneider, W.; Krumpl, G.; Mayer, N.; Raberger, G.

1987-01-01

323

Prevention of subsequent exercise-induced periinfarct ischemia by emergency coronary angioplasty in acute myocardial infarction: comparison with intracoronary streptokinase  

SciTech Connect

To compare the efficacy of emergency percutaneous transluminal coronary angioplasty and intracoronary streptokinase in preventing exercise-induced periinfarct ischemia, 28 patients presenting within 12 hours of the onset of symptoms of acute myocardial infarction were prospectively randomized. Of these, 14 patients were treated with emergency angioplasty and 14 patients received intracoronary streptokinase. Recatheterization and submaximal exercise thallium-201 single photon emission computed tomography were performed before hospital discharge. Periinfarct ischemia was defined as a reversible thallium defect adjacent to a fixed defect assessed qualitatively. Successful reperfusion was achieved in 86% of patients treated with emergency angioplasty and 86% of patients treated with intracoronary streptokinase (p = NS). Residual stenosis of the infarct-related coronary artery shown at predischarge angiography was 43.8 +/- 31.4% for the angioplasty group and 75.0 +/- 15.6% for the streptokinase group (p less than 0.05). Of the angioplasty group, 9% developed exercise-induced periinfarct ischemia compared with 60% of the streptokinase group (p less than 0.05). Thus, patients with acute myocardial infarction treated with emergency angioplasty had significantly less severe residual coronary stenosis and exercise-induced periinfarct ischemia than did those treated with intracoronary streptokinase. These results suggest further application of coronary angioplasty in the management of acute myocardial infarction.

Fung, A.Y.; Lai, P.; Juni, J.E.; Bourdillon, P.D.; Walton, J.A. Jr.; Laufer, N.; Buda, A.J.; Pitt, B.; O'Neill, W.W.

1986-09-01

324

Unravelling mitochondrial pathways to Parkinson's disease  

PubMed Central

Mitochondria are essential for cellular function due to their role in ATP production, calcium homeostasis and apoptotic signalling. Neurons are heavily reliant on mitochondrial integrity for their complex signalling, plasticity and excitability properties, and to ensure cell survival over decades. The maintenance of a pool of healthy mitochondria that can meet the bioenergetic demands of a neuron, is therefore of critical importance; this is achieved by maintaining a careful balance between mitochondrial biogenesis, mitochondrial trafficking, mitochondrial dynamics and mitophagy. The molecular mechanisms that underlie these processes are gradually being elucidated. It is widely recognized that mitochondrial dysfunction occurs in many neurodegenerative diseases, including Parkinson's disease. Mitochondrial dysfunction in the form of reduced bioenergetic capacity, increased oxidative stress and reduced resistance to stress, is observed in several Parkinson's disease models. However, identification of the recessive genes implicated in Parkinson's disease has revealed a common pathway involving mitochondrial dynamics, transport, turnover and mitophagy. This body of work has led to the hypothesis that the homeostatic mechanisms that ensure a healthy mitochondrial pool are key to neuronal function and integrity. In this paradigm, impaired mitochondrial dynamics and clearance result in the accumulation of damaged and dysfunctional mitochondria, which may directly induce neuronal dysfunction and death. In this review, we consider the mechanisms by which mitochondrial dysfunction may lead to neurodegeneration. In particular, we focus on the mechanisms that underlie mitochondrial homeostasis, and discuss their importance in neuronal integrity and neurodegeneration in Parkinson's disease. LINKED ARTICLES This article is part of a themed issue on Mitochondrial Pharmacology: Energy, Injury & Beyond. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2014.171.issue-8 PMID:24117181

Celardo, I; Martins, L M; Gandhi, S

2014-01-01

325

Dense-Core Secretory Granule Biogenesis  

NSDL National Science Digital Library

The dense-core secretory granule is a key organelle for secretion of hormones and neuropeptides in endocrine cells and neurons, in response to stimulation. Cholesterol and granins are critical for the assembly of these organelles at the trans-Golgi network, and their biogenesis is regulated quantitatively by posttranscriptional and posttranslational mechanisms.

Taeyoon Kim (National Institutes of Health Section on Cellular Neurobiology, National Institute of Child Health and Human Development); Marjorie C. Gondré-Lewis (National Institutes of Health Section on Cellular Neurobiology, National Institute of Child Health and Human Development); Irina Arnaoutova (National Institutes of Health Section on Cellular Neurobiology, National Institute of Child Health and Human Development); Y. Peng Loh (National Institutes of Health Section on Cellular Neurobiology, National Institute of Child Health and Human Development)

2006-04-01

326

Exercise-induced ST-elevation is related to left ventricular dysfunction but not to myocardial viability in patients with healed myocardial infarction  

Microsoft Academic Search

Background: Exercise-induced ST-segment elevation was proposed as a marker of myocardial viability after a recent myocardial infarction. Aims: The aim of this study was to evaluate whether exercise-induced ST segment elevation is related to viability or to left ventricular dysfunction in patients with history of old Q wave myocardial infarction. Methods: Fifty Ž. patients 43 men, age 57 11 years

Alain Manrique; Rene Koning; Anne Hitzel; Alain Cribier; Pierre Vera

327

Mitochondrial protein sorting as a therapeutic target for ATP synthase disorders  

PubMed Central

Mitochondrial diseases are systemic, prevalent and often fatal; yet treatments remain scarce. Identifying molecular intervention points that can be therapeutically targeted remains a major challenge, which we confronted via a screening assay we developed. Using yeast models of mitochondrial ATP synthase disorders, we screened a drug repurposing library, and applied genomic and biochemical techniques to identify pathways of interest. Here we demonstrate that modulating the sorting of nuclear-encoded proteins into mitochondria, mediated by the TIM23 complex, proves therapeutic in both yeast and patient-derived cells exhibiting ATP synthase deficiency. Targeting TIM23-dependent protein sorting improves an array of phenotypes associated with ATP synthase disorders, including biogenesis and activity of the oxidative phosphorylation machinery. Our study establishes mitochondrial protein sorting as an intervention point for ATP synthase disorders, and because of the central role of this pathway in mitochondrial biogenesis, it holds broad value for the treatment of mitochondrial diseases. PMID:25519239

Aiyar, Raeka S.; Bohnert, Maria; Duvezin-Caubet, Stéphane; Voisset, Cécile; Gagneur, Julien; Fritsch, Emilie S.; Couplan, Elodie; von der Malsburg, Karina; Funaya, Charlotta; Soubigou, Flavie; Courtin, Florence; Suresh, Sundari; Kucharczyk, Roza; Evrard, Justine; Antony, Claude; St.Onge, Robert P.; Blondel, Marc; di Rago, Jean-Paul; van der Laan, Martin; Steinmetz, Lars M.

2014-01-01

328

Mitochondrial Homeostasis Molecules: Regulation by a Trio of Recessive Parkinson's Disease Genes  

PubMed Central

Mitochondria are small organelles that produce the majority of cellular energy as ATP. Mitochondrial dysfunction has been implicated in the pathogenesis of Parkinson's disease (PD), and rare familial forms of PD provide valuable insight into the pathogenic mechanism underlying mitochondrial impairment, even though the majority of PD cases are sporadic. The regulation of mitochondria is crucial for the maintenance of energy-demanding neuronal functions in the brain. Mitochondrial biogenesis and mitophagic degradation are the major regulatory pathways that preserve optimal mitochondrial content, structure and function. In this mini-review, we provide an overview of the mitochondrial quality control mechanisms, emphasizing regulatory molecules in mitophagy and biogenesis that specifically interact with the protein products of three major recessive familial PD genes, PINK1, Parkin and DJ-1.

Han, Ji-Young; Kim, Ji-Soo

2014-01-01

329

Exercise-Induced Splanchnic Hypoperfusion Results in Gut Dysfunction in Healthy Men  

PubMed Central

Background Splanchnic hypoperfusion is common in various pathophysiological conditions and often considered to lead to gut dysfunction. While it is known that physiological situations such as physical exercise also result in splanchnic hypoperfusion, the consequences of flow redistribution at the expense of abdominal organs remained to be determined. This study focuses on the effects of splanchnic hypoperfusion on the gut, and the relationship between hypoperfusion, intestinal injury and permeability during physical exercise in healthy men. Methods and Findings Healthy men cycled for 60 minutes at 70% of maximum workload capacity. Splanchnic hypoperfusion was assessed using gastric tonometry. Blood, sampled every 10 minutes, was analyzed for enterocyte damage parameters (intestinal fatty acid binding protein (I-FABP) and ileal bile acid binding protein (I-BABP)). Changes in intestinal permeability were assessed using sugar probes. Furthermore, liver and renal parameters were assessed. Splanchnic perfusion rapidly decreased during exercise, reflected by increased gapg-apCO2 from ?0.85±0.15 to 0.85±0.42 kPa (p<0.001). Hypoperfusion increased plasma I-FABP (615±118 vs. 309±46 pg/ml, p<0.001) and I-BABP (14.30±2.20 vs. 5.06±1.27 ng/ml, p<0.001), and hypoperfusion correlated significantly with this small intestinal damage (rS?=?0.59; p<0.001). Last of all, plasma analysis revealed an increase in small intestinal permeability after exercise (p<0.001), which correlated with intestinal injury (rS?=?0.50; p<0.001). Liver parameters, but not renal parameters were elevated. Conclusions Exercise-induced splanchnic hypoperfusion results in quantifiable small intestinal injury. Importantly, the extent of intestinal injury correlates with transiently increased small intestinal permeability, indicating gut barrier dysfunction in healthy individuals. These physiological observations increase our knowledge of splanchnic hypoperfusion sequelae, and may help to understand and prevent these phenomena in patients. PMID:21811592

van Wijck, Kim; Lenaerts, Kaatje; van Loon, Luc J. C.; Peters, Wilbert H. M.; Buurman, Wim A.; Dejong, Cornelis H. C.

2011-01-01

330

Microarray analyses reveal novel targets of exercise-induced stress resistance in the dorsal raphe nucleus.  

PubMed

Serotonin (5-HT) is implicated in the development of stress-related mood disorders in humans. Physical activity reduces the risk of developing stress-related mood disorders, such as depression and anxiety. In rats, 6 weeks of wheel running protects against stress-induced behaviors thought to resemble symptoms of human anxiety and depression. The mechanisms by which exercise confers protection against stress-induced behaviors, however, remain unknown. One way by which exercise could generate stress resistance is by producing plastic changes in gene expression in the dorsal raphe nucleus (DRN). The DRN has a high concentration of 5-HT neurons and is implicated in stress-related mood disorders. The goal of the current experiment was to identify changes in the expression of genes that could be novel targets of exercise-induced stress resistance in the DRN. Adult, male F344 rats were allowed voluntary access to running wheels for 6 weeks; exposed to inescapable stress or no stress; and sacrificed immediately and 2 h after stressor termination. Laser capture micro dissection selectively sampled the DRN. mRNA expression was measured using the whole genome Affymetrix microarray. Comprehensive data analyses of gene expression included differential gene expression, log fold change (LFC) contrast analyses with False Discovery Rate correction, KEGG and Wiki Web Gestalt pathway enrichment analyses, and Weighted Gene Correlational Network Analysis (WGCNA). Our results suggest that physically active rats exposed to stress modulate expression of twice the number of genes, and display a more rapid and strongly coordinated response, than sedentary rats. Bioinformatics analyses revealed several potential targets of stress resistance including genes that are related to immune processes, tryptophan metabolism, and circadian/diurnal rhythms. PMID:23717271

Loughridge, Alice B; Greenwood, Benjamin N; Day, Heidi E W; McQueen, Matthew B; Fleshner, Monika

2013-01-01

331

Similarities between exercise-induced hypoalgesia and conditioned pain modulation in humans.  

PubMed

Pain inhibitory mechanisms are often assessed by paradigms of exercise-induced hypoalgesia (EIH) and conditioned pain modulation (CPM). In this study it was hypothesized that the spatial and temporal manifestations of EIH and CPM were comparable. The participants were 80 healthy subjects (40 females), between 18 and 65 years of age in this randomized, repeated-measures cross-over trial that involved data collection on 2 different days. CPM was assessed by 2 different cold pressor tests (hand and foot). EIH was assessed by 2 intensities of aerobic bicycling exercises and 2 intensities of isometric muscle contraction exercises (arm and leg). Pressure pain thresholds (PPTs) were recorded before, during, after, and 15 minutes after conditioning/exercise at sites local to and remote from the extremity used for cold pressor stimulation and exercise. PPTs increased at local as well as at remote sites during both cold pressor tests and after all of the exercise conditions except low-intensity bicycling. EIH after bicycling was higher in women than in men. CPM and the EIH responses after isometric exercises were comparable in men and women and were not affected by age. The EIH response was larger in the exercising body part compared with nonexercising body parts for all exercise conditions. High-intensity exercise produced greater EIH responses than did low-intensity exercise. The change in PPTs during cold pressor tests and the change in PPTs after exercises were not correlated. The CPM response was not dominated by local manifestations, and the effect was seen only during the stimulation, whereas exercise had larger local manifestations, and the effects were also found after exercise. PMID:24076045

Vaegter, Henrik Bjarke; Handberg, Gitte; Graven-Nielsen, Thomas

2014-01-01

332

Exercise-induced laryngeal obstruction: natural history and effect of surgical treatment.  

PubMed

The current follow-up study concerning the supraglottic type of exercise-induced laryngeal obstruction (EILO) was performed to reveal the natural history of supraglottic EILO and compare the symptoms, as well as the laryngeal function in conservatively versus surgically treated patients. A questionnaire-based survey was conducted 2-5 years after EILO was diagnosed by a continuous laryngoscopy exercise (CLE) test in 94 patients with a predominantly supraglottic obstruction. Seventy-one patients had been treated conservatively and 23 with laser supraglottoplasty. The questionnaire response rate was 70 and 100% in conservatively treated (CT) and surgically treated (ST) patients, respectively. A second CLE test was performed in 14 CT and 19 ST patients. A visual analogue scale on symptom severity indicated improvements in both the groups, i.e. mean values (± standard deviations) declined from 73 (20) to 53 (26) (P < 0.001) in the CT group and from 87 (26) to 25 (27) (P < 0.001) in the ST group. At follow-up, ST patients reported lower scores regarding current level of complaints, and higher ability to perform exercise, as well as to push themselves physically, all compared to CT patients (P < 0.001). CLE scores were normalized in 3 of 14 (21%) CT and 16 of 19 (84%) ST patients (Z = -3.6; P < 0.001). In conclusion, symptoms of EILO diagnosed in adolescents generally decreased during 2-5 years follow-up period but even more after the surgical treatment. Patients with supraglottic EILO may benefit from supraglottoplasty both as to laryngeal function and symptom relief. PMID:21643933

Maat, Robert Christiaan; Hilland, Magnus; Røksund, Ola Drange; Halvorsen, Thomas; Olofsson, Jan; Aarstad, Hans Jørgen; Heimdal, John-Helge

2011-10-01

333

Involvement of vascular endothelial growth factor in exercise induced bronchoconstriction in asthmatic patients  

PubMed Central

Background: There is evidence that the bronchial microcirculation has the potential to contribute to the pathophysiological mechanisms of exercise induced bronchoconstriction (EIB) in asthmatic subjects. Vascular endothelial growth factor (VEGF), which is highly expressed in asthmatic airways, increases vascular permeability. The relationship between VEGF levels in induced sputum and the severity of EIB in asthmatic subjects was studied. Methods: The concentration of VEGF in induced sputum was examined in 23 asthmatic subjects and 11 normal controls. The asthmatic subjects performed an exercise test and the % maximal fall in forced expiratory volume in 1 second (FEV1) was measured. Beclomethasone dipropionate (BDP) 400 µg twice daily was administered to the asthmatic subjects for 8 weeks and the exercise test and sputum induction were repeated. Results: The concentration of VEGF in induced sputum was significantly higher in asthmatic subjects than in normal controls. There was a significant correlation between the concentration of VEGF and the % maximal fall in FEV1 (r=0.826, p=0.0001) and between the concentration of VEGF and airway vascular permeability index (r=0.621, p=0.0037). After treatment with inhaled BDP there was a significant decrease in the concentration of VEGF in the asthmatic subjects (before treatment: 7051 (2361) pg/ml, after treatment: 4498 (2135) pg/ml, p<0.0001). The change in the concentration of VEGF was significantly correlated with the change in the % maximal fall in FEV1 (r=0.463, p=0.031). Conclusions: Excessive production of VEGF in asthmatic airways may contribute to the pathogenesis of EIB via increased airway vascular permeability. PMID:12324676

Kanazawa, H; Hirata, K; Yoshikawa, J

2002-01-01

334

Effects of allopurinol on exercise-induced muscle damage: new therapeutic approaches?  

PubMed

Intensive muscular activity can trigger oxidative stress, and free radicals may hence be generated by working skeletal muscle. The role of the enzyme xanthine oxidase as a generating source of free radicals is well documented and therefore is involved in the skeletal muscle damage as well as in the potential transient cardiovascular damage induced by high-intensity physical exercise. Allopurinol is a purine hypoxanthine-based structural analog and a well-known inhibitor of xanthine oxidase. The administration of the xanthine oxidase inhibitor allopurinol may hence be regarded as promising, safe, and an economic strategy to decrease transient skeletal muscle damage (as well as heart damage, when occurring) in top-level athletes when administered before a competition or a particularly high-intensity training session. Although continuous administration of allopurinol in high-level athletes is not recommended due to its possible role in hampering training-induced adaptations, the drug might be useful in non-athletes. Exertional rhabdomyolysis is the most common form of rhabdomyolysis and affects individuals participating in a type of intense exercise to which they are not accustomed. This condition can cause exercise-related myoglobinuria, thus increasing the risk of acute renal failure and is also associated with sickle cell trait. In this manuscript, we have reviewed the recent evidence about the effects of allopurinol on exercise-induced muscle damage. More research is needed to determine whether allopurinol may be useful for preventing not only exertional rhabdomyolysis and acute renal damage but also skeletal muscle wasting in critical illness as well as in immobilized, bedridden, sarcopenic or cachectic patients. PMID:25181966

Sanchis-Gomar, F; Pareja-Galeano, H; Perez-Quilis, C; Santos-Lozano, A; Fiuza-Luces, C; Garatachea, N; Lippi, G; Lucia, A

2015-01-01

335

Green tea extract supplementation gives protection against exercise-induced oxidative damage in healthy men.  

PubMed

The purpose of this study was to evaluate the effects of a long-term (4-week) green tea extract (GTE) supplementation in combination with strength training on selected blood markers of oxidative stress and muscular damage after a short-term exercise in previously untrained men. We hypothesized that GTE supplementation would elevate antioxidant potential and attenuate exercise-induced oxidative stress and muscular damage. Thirty-five male students were exposed to 4 weeks of strength training and received (in a randomized, double-blind design) GTE (n = 17; 640 mg polyphenols/d) or placebo (P; n = 18). Before (term I) and after 4 weeks of strength training and supplementation (term II), students performed a short-term muscular endurance test. Blood samples were collected at rest, 5 minutes after the muscular endurance test, and after 24 hours of recovery. Supplementation with GTE enhanced plasma total polyphenols at rest and 5 minutes after the muscular endurance test. Supplementation also contributed to the rise of resting total antioxidant status in plasma. Throughout the experiment (terms I and II), a reduction in plasma lipid hydroxyperoxides was observed 24 hours after the muscular endurance test. Four weeks of strength training resulted in an increase in plasma lipid hydroxyperoxides at rest, but only in the P group. In term I, the muscular endurance test induced an increase in activity of creatine kinase in plasma after 24 hours of recovery in both the P and GTE groups. In term II, plasma creatine kinase activity after 24 hours of recovery was elevated only in the P group. In conclusion, in previously untrained men, dietary supplementation with GTE (in combination with strength training) enhances the antioxidant defense system in plasma at rest and, in turn, may give protection against oxidative damage induced by both short-term muscular endurance test and long-term strength training. PMID:22118751

Jówko, Ewa; Sacharuk, Jaroslaw; Balasi?ska, Bozena; Ostaszewski, Piotr; Charmas, Malgorzata; Charmas, Robert

2011-11-01

336

Exercise-Induced Wheeze, Urgent Medical Visits, and Neighborhood Asthma Prevalence  

PubMed Central

OBJECTIVE: Exercise-induced wheeze (EIW) may identify a distinct population among asthmatics and give insight into asthma morbidity etiology. The prevalence of pediatric asthma and associated urgent medical visits varies greatly by neighborhood in New York City and is highest in low-income neighborhoods. Although increased asthma severity might contribute to the disparities in urgent medical visits, when controlling for health insurance coverage, we previously observed no differences in clinical measures of severity between asthmatic children living in neighborhoods with lower (3%–9%) versus higher (11%–19%) asthma prevalence. Among these asthmatics, we hypothesized that EIW would be associated with urgent medical visits and a child’s neighborhood asthma prevalence. METHODS: Families of 7- to 8-year-old children were recruited into a case-control study of asthma through an employer-based health insurance provider. Among the asthmatics (n = 195), prevalence ratios (PRs) for EIW were estimated. Final models included children with valid measures of lung function, seroatopy, and waist circumference (n = 140). RESULTS: EIW was associated with urgent medical visits for asthma (PR, 2.29; P = .021), independent of frequent wheeze symptoms. In contrast to frequent wheeze, EIW was not associated with seroatopy or exhaled NO, suggesting a distinct mechanism. EIW prevalence among asthmatics increased with increasing neighborhood asthma prevalence (PR, 1.09; P = .012), after adjustment for race, ethnicity, maternal asthma, environmental tobacco smoke, household income, and neighborhood income. CONCLUSIONS: EIW may contribute to the disparities in urgent medical visits for asthma between high- and low-income neighborhoods. Physicians caring for asthmatics should consider EIW an indicator of risk for urgent medical visits. PMID:23248227

Mainardi, Timothy R.; Mellins, Robert B.; Miller, Rachel L.; Acosta, Luis M.; Cornell, Alexandra; Hoepner, Lori; Quinn, James W.; Yan, Beizhan; Chillrud, Steven N.; Olmedo, Omar E.; Perera, Frederica P.; Goldstein, Inge F.; Rundle, Andrew G.; Jacobson, Judith S.

2013-01-01

337

EFFECTS OF MASSAGE ON MUSCULAR STRENGTH AND PROPRIOCEPTION AFTER EXERCISE-INDUCED MUSCLE DAMAGE.  

PubMed

Exercise-induced muscle damage (EIMD), which is commonly associated with eccentric exercise, unaccustomed exercise, and resistance training, may lead to delayed-onset muscle soreness, swelling, decreased muscle strength, and range of motion. Many researchers have evaluated various interventions to treat the signs and symptoms of EIMD. However, the effects of massage after EIMD are unclear. Here, we investigated the effect of massage on muscle strength and proprioception following EIMD. All subjects randomly were divided into a EIMD-treated control group (n = 10) and an massage-treated after EIMD experimental group (n = 11). EIMD was induced by repeated exercise. Massage treatment was provided by physiotherapist for a 15 min. It consists of light stroking, milking, friction, and skin rolling. Lactate was evaluated by lactate pro analyzer in pre and post exercise. Surface electromyography (muscle activity) and sonography (muscle thickness) were used to confirm the muscular characteristics. Proprioception was investigated by dual inclinometer. As a result, massage treatment on the gastrocnemius after EIMD increased activation of the medial gastrocnemius during contraction (p < 0.05). In the lateral and medial gastrocnemius, the ?s which is angle between muscle fibers and superficial aponeurosis showed a significant change (p < 0.05). However, there are no differences in the ?d which is angle between muscle fibers and deep aponeurosis. We also found that proprioceptive acuity in the ankle joint was significantly greater in the massage-treated experimental group compared to that in the control group (p < 0.05). These findings suggest that massage of the gastrocnemius after EIMD can improve muscle strength and proprioception by influencing the superficial layer of the gastrocnemius. PMID:25226328

Shin, Mal-Soon; Sung, Yun-Hee

2014-09-15

338

Vitamin D2 supplementation amplifies eccentric exercise-induced muscle damage in NASCAR pit crew athletes.  

PubMed

This study determined if 6-weeks vitamin D2 supplementation (vitD2, 3800 IU/day) had an influence on muscle function, eccentric exercise-induced muscle damage (EIMD), and delayed onset of muscle soreness (DOMS) in National Association for Stock Car Auto Racing (NASCAR) NASCAR pit crew athletes. Subjects were randomized to vitD2 (n=13) and placebo (n=15), and ingested supplements (double-blind) for six weeks. Blood samples were collected and muscle function tests conducted pre- and post-study (leg-back and hand grip dynamometer strength tests, body weight bench press to exhaustion, vertical jump, 30-s Wingate test). Post-study, subjects engaged in 90 min eccentric-based exercise, with blood samples and DOMS ratings obtained immediately after and 1- and 2-days post-exercise. Six weeks vitD2 increased serum 25(OH)D2 456% and decreased 25(OH)D3 21% versus placebo (p<0.001, p=0.036, respectively), with no influence on muscle function test scores. The post-study eccentric exercise bout induced EIMD and DOMS, with higher muscle damage biomarkers measured in vitD2 compared to placebo (myoglobin 252%, 122% increase, respectively, p=0.001; creatine phosphokinase 24 h post-exercise, 169%, 32%, p<0.001), with no differences for DOMS. In summary, 6-weeks vitD2 (3800 IU/day) significantly increased 25(OH)D2 and decreased 25(OH)D3, had no effect on muscle function tests, and amplified muscle damage markers in NASCAR pit crew athletes following eccentric exercise. PMID:24362707

Nieman, David C; Gillitt, Nicholas D; Shanely, R Andrew; Dew, Dustin; Meaney, Mary Pat; Luo, Beibei

2014-01-01

339

Resistance exercise-induced fluid shifts: change in active muscle size and plasma volume  

NASA Technical Reports Server (NTRS)

The purpose of this study was to test the hypothesis that the reduction in plasma volume (PV) induced by resistance exercise reflects fluid loss to the extravascular space and subsequently selective increase in cross-sectional area (CSA) of active but not inactive skeletal muscle. We compared changes in active and inactive muscle CSA and PV after barbell squat exercise. Magnetic resonance imaging (MRI) was used to quantify muscle involvement in exercise and to determine CSA of muscle groups or individual muscles [vasti (VS), adductor (Add), hamstring (Ham), and rectus femoris (RF)]. Muscle involvement in exercise was determined using exercise-induced contrast shift in spin-spin relaxation time (T2)-weighted MR images immediately postexercise. Alterations in muscle size were based on the mean CSA of individual slices. Hematocrit, hemoglobin, and Evans blue dye were used to estimate changes in PV. Muscle CSA and PV data were obtained preexercise and immediately postexercise and 15 and 45 min thereafter. A hierarchy of muscle involvement in exercise was found such that VS > Add > Ham > RF, with the Ham and RF showing essentially no involvement. CSA of the VS and Add muscle groups were increased 10 and 5%, respectively, immediately after exercise in each thigh with no changes in Ham and RF CSA. PV was decreased 22% immediately following exercise. The absolute loss of PV was correlated (r2 = 0.75) with absolute increase in muscle CSA immediately postexercise, supporting the notion that increased muscle size after resistance exercise reflects primarily fluid movement from the vascular space into active but not inactive muscle.

Ploutz-Snyder, L. L.; Convertino, V. A.; Dudley, G. A.

1995-01-01

340

Acute Whole-Body Cooling for Exercise-Induced Hyperthermia: A Systematic Review  

PubMed Central

Objective: To assess existing original research addressing the efficiency of whole-body cooling modalities in the treatment of exertional hyperthermia. Data Sources: During April 2007, we searched MEDLINE, EMBASE, Scopus, SportDiscus, CINAHL, and Cochrane Reviews databases as well as ProQuest for theses and dissertations to identify research studies evaluating whole-body cooling treatments without limits. Key words were cooling, cryotherapy, water immersion, cold-water immersion, ice-water immersion, icing, fanning, bath, baths, cooling modality, heat illness, heat illnesses, exertional heatstroke, exertional heat stroke, heat exhaustion, hyperthermia, hyperthermic, hyperpyrexia, exercise, exertion, running, football, military, runners, marathoner, physical activity, marathoning, soccer, and tennis. Data Synthesis: Two independent reviewers graded each study on the Physiotherapy Evidence Database (PEDro) scale. Seven of 89 research articles met all inclusion criteria and a minimum score of 4 out of 10 on the PEDro scale. Conclusions: After an extensive and critical review of the available research on whole-body cooling for the treatment of exertional hyperthermia, we concluded that ice-water immersion provides the most efficient cooling. Further research comparing whole-body cooling modalities is needed to identify other acceptable means. When ice-water immersion is not possible, continual dousing with water combined with fanning the patient is an alternative method until more advanced cooling means can be used. Until future investigators identify other acceptable whole-body cooling modalities for exercise-induced hyperthermia, ice-water immersion and cold-water immersion are the methods proven to have the fastest cooling rates. PMID:19180223

McDermott, Brendon P; Casa, Douglas J; Ganio, Matthew S; Lopez, Rebecca M; Yeargin, Susan W; Armstrong, Lawrence E; Maresh, Carl M

2009-01-01

341

Impaired mitochondrial function in human placenta with increased maternal adiposity.  

PubMed

The placenta plays a key role in regulation of fetal growth and development and in mediating in utero developmental programming. Obesity, which is associated with chronic inflammation and mitochondrial dysfunction in many tissues, exerts a programming effect in pregnancy. We determined the effect of increasing maternal adiposity and of fetal sex on placental ATP generation, mitochondrial biogenesis, expression of electron transport chain subunits, and mitochondrial function in isolated trophoblasts. Placental tissue was collected from women with prepregnancy BMI ranging from 18.5 to 45 following C-section at term with no labor. Increasing maternal adiposity was associated with excessive production of reactive oxygen species and a significant reduction in placental ATP levels in placentae with male and female fetuses. To explore the potential mechanism of placental mitochondrial dysfunction, levels of transcription factors regulating the expression of genes involved in electron transport and mitochondrial biogenesis were measured. Our in vitro studies showed significant reduction in mitochondrial respiration in cultured primary trophoblasts with increasing maternal obesity along with an abnormal metabolic flexibility of these cells. This reduction in placental mitochondrial respiration in pregnancies complicated by maternal obesity could compromise placental function and potentially underlie the increased susceptibility of these pregnancies to fetal demise in late gestation and to developmental programming. PMID:25028397

Mele, James; Muralimanoharan, Sribalasubashini; Maloyan, Alina; Myatt, Leslie

2014-09-01

342

Insulin-Resistant Heart Exhibits a Mitochondrial Biogenic Response Driven by the Peroxisome Proliferator-Activated Receptor-?/PGC-1? Gene Regulatory Pathway  

PubMed Central

Background Obesity and diabetes mellitus are complex metabolic problems of pandemic proportion, contributing to significant cardiovascular mortality. Recent studies have shown altered mitochondrial function in the hearts of diabetic animals. We hypothesized that regulatory events involved in the control of mitochondrial function are activated in the prediabetic, insulin-resistant stage. Methods and Results Morphometric analyses demonstrated that cardiac myocyte mitochondrial volume density was increased in insulin-resistant uncoupling protein-diptheria toxin A (UCP-DTA) transgenic mice, a murine model of metabolic syndrome, compared with littermate controls. Mitochondrial DNA content and expression of genes involved in multiple mitochondrial pathways were also increased in insulin-resistant UCP-DTA hearts. The nuclear receptor, peroxisome proliferator-activated receptor-? (PPAR?), is known to activate metabolic genes in the diabetic heart. Therefore, we evaluated the role of PPAR? in the observed mitochondrial biogenesis response in the insulin-resistant heart. Insulin-resistant UCP-DTA mice crossed into a PPAR?-null background did not exhibit evidence of mitochondrial biogenesis or induction of mitochondrial gene expression. Conversely, transgenic mice with cardiac-specific overexpression of PPAR? exhibited signatures of cardiac mitochondrial biogenesis. A screen for candidate mediators of the PPAR?-driven mitochondrial biogenic response revealed that expression of PPAR? coactivator-1? (PGC-1?), a known regulator of mitochondrial biogenesis, was activated in wild-type UCP-DTA mice but not in PPAR?-deficient UCP-DTA mice. Conclusions These results demonstrate that mitochondrial biogenesis occurs early in the development of diabetic cardiac dysfunction through a transcriptional regulatory circuit that involves activation of PGC-1? gene expression by the fatty acid–activated nuclear receptor PPAR?. PMID:17261654

Duncan, Jennifer G.; Fong, Juliet L.; Medeiros, Denis M.; Finck, Brian N.; Kelly, Daniel P.

2015-01-01

343

Caenorhabditis elegans neuron degeneration and mitochondrial suppression caused by selected environmental chemicals  

PubMed Central

Mitochondrial alterations have been documented for many years in the brains of Parkinson’s disease (PD), a disorder that is characterized by the selective loss of dopamine neurons. Recent studies have demonstrated that Parkinson’s disease-associated proteins are either present in mitochondria or translocated into mitochondria in response to stress, further reinforcing the importance of the mitochondrial function in the pathogenesis of Parkinson’s disease. Exposure to environmental chemicals such as pesticides and heavy metals has been suggested as risk factors in the development of Parkinson’s disease. It has been reported that a number of environmental agents including tobacco smoke and perfluorinated compounds, pesticides, as well as metals (Mn2+ and Pb2+) modulate mitochondrial function. However the exact mechanism of mitochondrial alteration has not been defined in the context of the development and progression of Parkinson’s disease. The complexity of the mammalian system has made it difficult to dissect the molecular components involved in the pathogenesis of Parkinson’s disease. In the present study we used the nematode Caenorhabditis elegans (C. elegans) model of neuron degeneration and investigated the effect of environmental chemicals on mitochondrial biogenesis and mitochondrial gene regulation. Chronic exposure to low concentration (2 or 4 ?M) of pesticide rotenone, resulted in significant loss of dopamine neuron in C. elegans, a classic feature of Parkinson’s disease. We then determined if the rotenone-induced neuron degeneration is accompanied by a change in mitochondria biogenesis. Analysis of mitochondrial genomic replication by quantitative PCR showed a dramatic decrease in mitochondrial DNA (mtDNA) copies of rotenone-treated C. elegans compared to control. This decreased mitochondrial biogenesis occurred prior to the development of loss of dopamine neurons, and was persistent. The inhibition of mtDNA replication was also found in C. elegans exposed to another neuron toxicant Mn2+ at the concentration 50 or 100 mM. We further examined the mitochondrial gene expression and found significant lower level of mitochondrial complex IV subunits COI and COII in C. elegans exposed to rotenone. These results demonstrate that environmental chemicals cause persistent suppression of mitochondrial biogenesis and mitochondrial gene expression, and suggest a critical role of modifying mitochondrial biogenesis in toxicants-induced neuron degeneration in C. elegans model. PMID:24380023

Zhou, Shaoyu; Wang, Zemin; Klaunig, James E

2013-01-01

344

Loss of mitochondrial exo/endonuclease EXOG affects mitochondrial respiration and induces ROS-mediated cardiomyocyte hypertrophy.  

PubMed

Recently, a locus at the mitochondrial exo/endonuclease EXOG gene, which has been implicated in mitochondrial DNA repair, was associated with cardiac function. The function of EXOG in cardiomyocytes is still elusive. Here we investigated the role of EXOG in mitochondrial function and hypertrophy in cardiomyocytes. Depletion of EXOG in primary neonatal rat ventricular cardiomyocytes (NRVCs) induced a marked increase in cardiomyocyte hypertrophy. Depletion of EXOG, however, did not result in loss of mitochondrial DNA integrity. Although EXOG depletion did not induce fetal gene expression and common hypertrophy pathways were not activated, a clear increase in ribosomal S6 phosphorylation was observed, which readily explains increased protein synthesis. With the use of a Seahorse flux analyzer, it was shown that the mitochondrial oxidative consumption rate (OCR) was increased 2.4-fold in EXOG-depleted NRVCs. Moreover, ATP-linked OCR was 5.2-fold higher. This increase was not explained by mitochondrial biogenesis or alterations in mitochondrial membrane potential. Western blotting confirmed normal levels of the oxidative phosphorylation (OXPHOS) complexes. The increased OCR was accompanied by a 5.4-fold increase in mitochondrial ROS levels. These increased ROS levels could be normalized with specific mitochondrial ROS scavengers (MitoTEMPO, mnSOD). Remarkably, scavenging of excess ROS strongly attenuated the hypertrophic response. In conclusion, loss of EXOG affects normal mitochondrial function resulting in increased mitochondrial respiration, excess ROS production, and cardiomyocyte hypertrophy. PMID:25377088

Tigchelaar, Wardit; Yu, Hongjuan; de Jong, Anne Margreet; van Gilst, Wiek H; van der Harst, Pim; Westenbrink, B Daan; de Boer, Rudolf A; Silljé, Herman H W

2015-01-15

345

Enantiomeric Natural Products: Occurrence and Biogenesis**  

PubMed Central

In Nature, chiral natural products are usually produced in optically pure form; however, on occasion Nature is known to produce enantiomerically opposite metabolites. These enantiomeric natural products can arise in Nature from a single species, or from different genera and/or species. Extensive research has been carried out over the years in an attempt to understand the biogenesis of naturally occurring enantiomers, however, many fascinating puzzles and stereochemical anomalies still remain. PMID:22555867

Finefield, Jennifer M.; Sherman, David H.; Kreitman, Martin; Williams, Robert M.

2012-01-01

346

Exercise-induced arterial hypoxaemia and the mechanics of breathing in healthy young women  

PubMed Central

The purpose of this study was to characterize exercise-induced arterial hypoxaemia (EIAH), pulmonary gas exchange and respiratory mechanics during exercise, in young healthy women. We defined EIAH as a >10 mmHg decrease in arterial oxygen tension () during exercise compared to rest. We used a heliox inspirate to test the hypothesis that mechanical constraints contribute to EIAH. Subjects with a spectrum of aerobic capacities (n= 30; maximal oxygen consumption () = 49 ± 1, range 28–62 ml kg?1 min?1) completed a stepwise treadmill test and a subset (n= 18 with EIAH) completed a constant load test (?85%) with heliox gas. Throughout exercise arterial blood gases, oxyhaemoglobin saturation (), the work of breathing (WOB) and expiratory flow limitation (EFL) were assessed. Twenty of the 30 women developed EIAH with a nadir and ranging from 58 to 88 mmHg and 87 to 96%, respectively. At maximal exercise, was inversely related to (r=–0.57, P < 0.05) with notable exceptions where some subjects with low aerobic fitness levels demonstrated EIAH. Subjects with EIAH had a greater (51 ± 1 vs. 43 ± 2 ml kg?1 min?1), lower end-exercise (93.2 ± 0.5 vs. 96.1 ± 0.3%) and a greater maximal energetic WOB (324 ± 19 vs. 247 ± 23 J min?1), but had similar resting pulmonary function compared to those without EIAH. Most subjects developed EIAH at submaximal exercise intensities, with distinct patterns of hypoxaemia. In some subjects with varying aerobic fitness levels, mechanical ventilatory constraints (i.e. EFL) were the primary mechanism associated with the hypoxaemia during the maximal test. Mechanical ventilatory constraints also prevented adequate compensatory alveolar hyperventilation in most EIAH subjects. Minimizing mechanical ventilatory constraints with heliox inspiration partially reversed EIAH in subjects who developed EFL. In conclusion, healthy women of all aerobic fitness levels can develop EIAH and begin to do so at submaximal intensities. Mechanical ventilatory constraints are a primary mechanism for EIAH in some healthy women and prevent reversal of hypoxaemia in women for whom it is not the primary mechanism. PMID:23587886

Dominelli, Paolo B; Foster, Glen E; Dominelli, Giulio S; Henderson, William R; Koehle, Michael S; McKenzie, Donald C; Sheel, A William

2013-01-01

347

Electromyographic Activity of the Biceps Brachii After Exercise-Induced Muscle Damage  

PubMed Central

It is well known that strenuous eccentric exercise may result in muscle damage. We proposed that vigorous eccentric exercise (EE) would impair myoelectric activity of the biceps brachii. This study utilised a 7-day prospective time-series design. Ten healthy males performed a session of 70 maximal EE elbow flexion contractions. Analysis of surface electromyography activity (sEMG) was performed on the signals recorded during isometric contractions at 50% (IC50) and 80% (IC80) of maximum voluntary isometric torque (MVT), deriving RMS and MDF as sEMG parameters. Linear regression of the RMS and MDF time-series (20-s sustained IC50 and IC80) was used to extract intercepts and slopes of these signals on each day. Plasma creatine kinase activity (CK), MVT, arm circumference, subjective perception of soreness and elbow joint range of motion were also measured to assess effectiveness of EE to evoke muscle damage. CK increased over resting values until day 5 after EE, and remained significantly (p < 0.05) elevated even on day 7. MVT had decreased to 45% of its initial value by day 2 after EE, and remained significantly depressed for the following 6 days. In addition, muscle soreness and arm circumference increased, and range of motion decreased after EE. A significant shift of MDF intercept towards lower frequencies at both IC50 and IC80 was observed after EE in the exercised arm, and these values gradually recovered within the next 3 days during IC50. Although there were some changes in RMS values, these alterations were persistent in both control and exercised arms, and did not follow a consistent pattern. In conclusion, a prolonged reduction in MDF intercept was observed after EE, but this was not closely time-associated with the biochemical, anthropometric or functional markers of muscle damage. Compared to RMS, MDF was a more consistent measure to reflect changes in sEMG. Key pointsEMG can be a useful tool to detect exercise-induced muscle damage,MDF decreased after eccentric exercise,This decrease could be related to a reduction in the recruitment of fast twitch fibres, andCompared to RMS, MDF was a more consistent parameter to reflect the changes in EMG after eccentric exercise. PMID:24149479

Ahmadi, Sirous; Sinclair, Peter J.; Foroughi, Nasim; Davis, Glen M.

2007-01-01

348

Erythropoietin Activates Mitochondrial Biogenesis and Couples Red Cell Mass to Mitochondrial Mass in the Heart  

EPA Science Inventory

RATIONALE: Erythropoietin (EPO) is often administered to cardiac patients with anemia, particularly from chronic kidney disease, and stimulation of erythropoiesis may stabilize left ventricular and renal function by recruiting protective effects beyond the correction of anemia. O...

349

[Wheat dependent exercise induced anaphylaxis possibly sensitized by the hydrolyzed wheat proteins in a facial cleansing soap].  

PubMed

There are increasing cases of wheat dependent exercise-induced anaphylaxis (WDEIA) with transcutaneous or transmucosal sensitization. Hydrolyzed wheat included in a certain brand of soap was identified as a cause of sensitization. The useful clues to detect this disorder consist of the patient's past usage of a soap containing hydrolyzed wheat, the appearance of cutaneous or mucosal symptoms after the intake of wheat or washing with this soap, and a high level of specific IgE for wheat gluten. Because hydrolyzed wheat is used as an additive in a wide variety of cosmetics, we should pay careful attention to the ingredients of cosmetics when observing WDEIA. PMID:22428462

Kobayashi, Miwa; Okura, Risa; Yoshioka, Haruna; Hiromasa, Kana; Yoshioka, Manabu; Nakamura, Motonobu

2012-03-01

350

Development of pharmacological strategies for mitochondrial disorders  

PubMed Central

Mitochondrial diseases are an unusually genetically and phenotypically heterogeneous group of disorders, which are extremely challenging to treat. Currently, apart from supportive therapy, there are no effective treatments for the vast majority of mitochondrial diseases. Huge scientific effort, however, is being put into understanding the mechanisms underlying mitochondrial disease pathology and developing potential treatments. To date, a variety of treatments have been evaluated by randomized clinical trials, but unfortunately, none of these has delivered breakthrough results. Increased understanding of mitochondrial pathways and the development of many animal models, some of which are accurate phenocopies of human diseases, are facilitating the discovery and evaluation of novel prospective treatments. Targeting reactive oxygen species has been a treatment of interest for many years; however, only in recent years has it been possible to direct antioxidant delivery specifically into the mitochondria. Increasing mitochondrial biogenesis, whether by pharmacological approaches, dietary manipulation or exercise therapy, is also currently an active area of research. Modulating mitochondrial dynamics and mitophagy and the mitochondrial membrane lipid milieu have also emerged as possible treatment strategies. Recent technological advances in gene therapy, including allotopic and transkingdom gene expression and mitochondrially targeted transcription activator-like nucleases, have led to promising results in cell and animal models of mitochondrial diseases, but most of these techniques are still far from clinical application. Linked Articles This article is part of a themed issue on Mitochondrial Pharmacology: Energy, Injury & Beyond. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2014.171.issue-8 PMID:24116962

Kanabus, M; Heales, S J; Rahman, S

2014-01-01

351

Sequence-specific Interaction between Mitochondrial Fe-S Scaffold Protein Isu and Hsp70 Ssq1 Is Essential for Their in Vivo Function*  

E-print Network

Sequence-specific Interaction between Mitochondrial Fe-S Scaffold Protein Isu and Hsp70 Ssq1 of Fe-S clusters in the yeast mitochondrial matrix, is a substrate protein for the Hsp70 Ssq1 and the J proteins. We conclude that the Ssq1-Isu substrate interaction is critical for Fe-S cluster biogenesis

Craig, Elizabeth A

352

Absence of the Mitochondrial AAA Protease Yme1p Restores F0-ATPase Subunit Accumulation in an oxa1 Deletion Mutant  

E-print Network

Absence of the Mitochondrial AAA Protease Yme1p Restores F0-ATPase Subunit Accumulation in an oxa1 The nuclear gene OXA1 encodes a protein located within the mitochondrial inner membrane that is re- quired for the biogenesis of both cytochrome c oxidase (Cox) and ATPase. In the absence of Oxa1p, the translo- cation

Meier, Iris

353

Abnormal Synaptic Vesicle Biogenesis in Drosophila Synaptogyrin Mutants  

E-print Network

Sustained neuronal communication relies on the coordinated activity of multiple proteins that regulate synaptic vesicle biogenesis and cycling within the presynaptic terminal. Synaptogyrin and synaptophysin are conserved ...

Stevens, Robin Jean

354

Targeted expression of catalase to mitochondria prevents age-associated reductions in mitochondrial function and insulin resistance.  

PubMed

Aging-associated muscle insulin resistance has been hypothesized to be due to decreased mitochondrial function, secondary to cumulative free radical damage, leading to increased intramyocellular lipid content. To directly test this hypothesis, we examined both in vivo and in vitro mitochondrial function, intramyocellular lipid content, and insulin action in lean healthy mice with targeted overexpression of the human catalase gene to mitochondria (MCAT mice). Here, we show that MCAT mice are protected from age-induced decrease in muscle mitochondrial function (?30%), energy metabolism (?7%), and lipid-induced muscle insulin resistance. This protection from age-induced reduction in mitochondrial function was associated with reduced mitochondrial oxidative damage, preserved mitochondrial respiration and muscle ATP synthesis, and AMP-activated protein kinase-induced mitochondrial biogenesis. Taken together, these data suggest that the preserved mitochondrial function maintained by reducing mitochondrial oxidative damage may prevent age-associated whole-body energy imbalance and muscle insulin resistance. PMID:21109199

Lee, Hui-Young; Choi, Cheol Soo; Birkenfeld, Andreas L; Alves, Tiago C; Jornayvaz, Francois R; Jurczak, Michael J; Zhang, Dongyan; Woo, Dong Kyun; Shadel, Gerald S; Ladiges, Warren; Rabinovitch, Peter S; Santos, Janine H; Petersen, Kitt F; Samuel, Varman T; Shulman, Gerald I

2010-12-01

355

Targeted Expression of Catalase to Mitochondria Prevents Age-Associated Reductions in Mitochondrial Function and Insulin Resistance  

PubMed Central

SUMMARY Aging-associated muscle insulin resistance has been hypothesized to be due to decreased mitochondrial function, secondary to cumulative free radical damage, leading to increased intramyocellular lipid content. To directly test this hypothesis we examined both in vivo and in vitro mitochondrial function, intramyocellular lipid content and insulin action in lean healthy mice with targeted overexpression of the human catalase gene to mitochondria (MCAT mice). Here we show that MCAT mice are protected from age-induced decrease in muscle mitochondrial function (~30%), energy metabolism (~7%) and lipid-induced muscle insulin resistance. This protection from age-induced reduction in mitochondrial function was associated with reduced mitochondrial oxidative damage, preserved mitochondrial respiration and muscle ATP synthesis and AMP-activated protein kinase-induced mitochondrial biogenesis. Taken together these data suggest that the preserved mitochondrial function maintained by reducing mitochondrial oxidative damage may prevent age-associated whole body energy imbalance and muscle insulin resistance. PMID:21109199

Lee, Hui-Young; Choi, Cheol Soo; Birkenfeld, Andreas L.; Alves, Tiago C.; Jornayvaz, Francois R.; Jurczak, Michael J.; Zhang, Dongyan; Woo, Dong Kyun; Shadel, Gerald S.; Ladiges, Warren; Rabinovitch, Peter S.; Santos, Janine H.; Petersen, Kitt F.; Samuel, Varman T.; Shulman, Gerald I.

2010-01-01

356

p21{sup WAF1/CIP1} deficiency induces mitochondrial dysfunction in HCT116 colon cancer cells  

SciTech Connect

Highlights: Black-Right-Pointing-Pointer p21{sup -/-} HCT116 cells exhibited an increase in mitochondrial mass. Black-Right-Pointing-Pointer The expression levels of PGC-1{alpha} and AMPK were upregulated in p21{sup -/-} HCT116 cells. Black-Right-Pointing-Pointer The proliferation of p21{sup -/-} HCT116 cells in galactose medium was significantly impaired. Black-Right-Pointing-Pointer p21 may play a role in maintaining proper mitochondrial mass and respiratory function. -- Abstract: p21{sup WAF1/CIP1} is a critical regulator of cell cycle progression. However, the role of p21 in mitochondrial function remains poorly understood. In this study, we examined the effect of p21 deficiency on mitochondrial function in HCT116 human colon cancer cells. We found that there was a significant increase in the mitochondrial mass of p21{sup -/-} HCT116 cells, as measured by 10-N-nonyl-acridine orange staining, as well as an increase in the mitochondrial DNA content. In contrast, p53{sup -/-} cells had a mitochondrial mass comparable to that of wild-type HCT116 cells. In addition, the expression levels of the mitochondrial biogenesis regulators PGC-1{alpha} and TFAM and AMPK activity were also elevated in p21{sup -/-} cells, indicating that p21 deficiency induces the rate of mitochondrial biogenesis through the AMPK-PGC-1{alpha} axis. However, the increase in mitochondrial biogenesis in p21{sup -/-} cells did not accompany an increase in the cellular steady-state level of ATP. Furthermore, p21{sup -/-} cells exhibited significant proliferation impairment in galactose medium, suggesting that p21 deficiency induces a defect in the mitochondrial respiratory chain in HCT116 cells. Taken together, our results suggest that the loss of p21 results in an aberrant increase in the mitochondrial mass and in mitochondrial dysfunction in HCT116 cells, indicating that p21 is required to maintain proper mitochondrial mass and respiratory function.

Kim, Ae Jeong; Jee, Hye Jin; Song, Naree; Kim, Minjee [Department of Biochemistry, College of Medicine, Dong-A University, Busan (Korea, Republic of) [Department of Biochemistry, College of Medicine, Dong-A University, Busan (Korea, Republic of); Mitochondria Hub Regulation Center, College of Medicine, Dong-A University, Busan (Korea, Republic of); Jeong, Seon-Young [Mitochondria Hub Regulation Center, College of Medicine, Dong-A University, Busan (Korea, Republic of) [Mitochondria Hub Regulation Center, College of Medicine, Dong-A University, Busan (Korea, Republic of); Department of Medical Genetics, Ajou University School of Medicine (Korea, Republic of); Yun, Jeanho, E-mail: yunj@dau.ac.kr [Department of Biochemistry, College of Medicine, Dong-A University, Busan (Korea, Republic of) [Department of Biochemistry, College of Medicine, Dong-A University, Busan (Korea, Republic of); Mitochondria Hub Regulation Center, College of Medicine, Dong-A University, Busan (Korea, Republic of)

2013-01-11

357

Fatty Acid Synthase as a Factor Required for Exercise-Induced Cognitive Enhancement and Dentate Gyrus Cellular Proliferation  

PubMed Central

Voluntary running is a robust inducer of adult hippocampal neurogenesis. Given that fatty acid synthase (FASN), the key enzyme for de novo fatty acid biosynthesis, is critically involved in proliferation of embryonic and adult neural stem cells, we hypothesized that FASN could mediate both exercise-induced cell proliferation in the subgranular zone (SGZ) of the dentate gyrus (DG) and enhancement of spatial learning and memory. In 20 week-old male mice, voluntary running-induced hippocampal-specific upregulation of FASN was accompanied also by hippocampal-specific accumulation of palmitate and stearate saturated fatty acids. In experiments addressing the functional role of FASN in our experimental model, chronic intracerebroventricular (i.c.v.) microinfusions of C75, an irreversible FASN inhibitor, and significantly impaired exercise-mediated improvements in spatial learning and memory in the Barnes maze. Unlike the vehicle-injected mice, the C75 group adopted a non-spatial serial escape strategy and displayed delayed escape latencies during acquisition and memory tests. Furthermore, pharmacologic blockade of FASN function with C75 resulted in a significant reduction, compared to vehicle treated controls, of the number of proliferative cells in the DG of running mice as measured by immunoreactive to Ki-67 in the SGZ. Taken together, our data suggest that FASN plays an important role in exercise-mediated cognitive enhancement, which might be associated to its role in modulating exercise-induced stimulation of neurogenesis. PMID:24223732

Chorna, Nataliya E.; Santos-Soto, Iván J.; Carballeira, Nestor M.; Morales, Joan L.; de la Nuez, Janneliz; Cátala-Valentin, Alma; Chornyy, Anatoliy P.; Vázquez-Montes, Adrinel; De Ortiz, Sandra Peña

2013-01-01

358

Endogenous Cannabinoid Signaling Is Required for Voluntary Exercise-induced Enhancement of Progenitor Cell Proliferation in the Hippocampus  

PubMed Central

Voluntary exercise and endogenous cannabinoid activity have independently been shown to regulate hippocampal plasticity. The aim of the current study was to determine whether the endocannabinoid system is regulated by voluntary exercise and if these changes contribute to exercise-induced enhancement of cell proliferation. In Experiment 1, eight days of free access to a running wheel increased the agonist binding site density of the cannabinoid CB1 receptor; CB1 receptor-mediated GTP?S binding; and the tissue content of the endocannabinoid anandamide in the hippocampus but not in the prefrontal cortex. In Experiment 2, the CB1 receptor antagonist AM251 (1 mg/kg) was administered daily to animals given free access to a running wheel for 8 days, after which cell proliferation in the hippocampus was examined through immunohistochemical analysis of the cell cycle protein Ki-67. Voluntary exercise increased proliferation of progenitor cells, as evidenced by the increase in the number of Ki-67 positive cells in the granule cell layer of the dentate gyrus in the hippocampus. However, this effect was abrogated by concurrent treatment with AM251, indicating that the increase in endocannabinoid signaling in the hippocampus is required for the exercise-induced increase in cell proliferation. These data demonstrate that the endocannabinoid system in the hippocampus is sensitive to environmental change and suggest that it is a mediator of experience-induced plasticity. PMID:19489006

Hill, Matthew N.; Titterness, Andrea K.; Morrish, Anna C.; Carrier, Erica J.; Lee, Tiffany T.-Y.; Gil-Mohapel, Joana; Gorzalka, Boris B.; Hillard, Cecilia J.; Christie, Brian R.

2009-01-01

359

The protective effects of a polyphenol-enriched protein powder on exercise-induced susceptibility to virus infection.  

PubMed

Prolonged and intensive exercise induces transient immunosuppression and is associated with an increased risk and severity of infections. The goal of this study was to characterize the antiviral and antibacterial properties of the bioactive metabolites of a blueberry-green tea-polyphenol soy protein complex (PSPC) in the serum of supplemented subjects during a 3-day intensified training period. Long-distance runners, randomly divided into two groups, ingested 40?g/day PSPC or placebo (soy protein and colorings) for 17?days, with a 3-day running period inserted at day 14. Blood serum samples were collected pre-14?days and post-14?days supplementation, and immediately and 14?h after the third day of running. The post-exercise serum from both groups significantly promoted the growth of Escherichia coli and Staphylococcus aureus in culture by 20-70%, but returned to normal levels following recovery. Furthermore, the serum from subjects ingesting PSPC did not display antibacterial properties at any time point. In contrast, there was a significant difference in the ability of serum from PSPC-supplemented versus placebo-supplemented athletes to protect cells in culture from killing by vesicular stomatitis virus following strenuous exercise. In addition, the serum of subjects who ingested PSPC significantly delayed an exercise-induced increase in virus replication. These results indicate that polyphenol complexes containing blueberry and green tea have the potential to protect athletes from virus infections following rigorous exercise. Copyright © 2014 John Wiley & Sons, Ltd. PMID:25088029

Ahmed, Maryam; Henson, Dru A; Sanderson, Matthew C; Nieman, David C; Gillitt, Nicholas D; Lila, Mary Ann

2014-12-01

360

Murine double minute-2 expression is required for capillary maintenance and exercise-induced angiogenesis in skeletal muscle.  

PubMed

Exercise-induced angiogenesis is a key determinant of skeletal muscle function. Here, we investigated whether the E3 ubiquitin ligase murine double minute-2 (Mdm2) exerts a proangiogenic function in exercised skeletal muscle. Mdm2 hypomorphic (Mdm2(Puro/?7-9)) mice have a 60% reduction in Mdm2 expression compared with that in wild-type animals. Capillary staining on muscle sections from Mdm2(Puro/?7-9) sedentary mice with a wild-type or knockout background for p53 revealed that deficiency in Mdm2 resulted in 20% capillary regression independently of p53 status. In response to one bout of exercise, protein expression of the proangiogenic vascular endothelial growth factor-A (VEGF-A) was increased by 64% in muscle from wild-type animals, and endothelial cell outgrowth from exercised muscle biopsy samples cultured in a 3-dimensional collagen gel was enhanced by 37%. These proangiogenic responses to exercise were impaired in exercised Mdm2(Puro/?7-9) mice. Prolonged exercise training resulted in increased Mdm2 protein expression (+49%) and capillarization (+24%) in wild-type muscles. However, exercise training-induced angiogenesis was abolished in Mdm2(Puro/?7-9) mice. Finally, exercise training restored Mdm2, VEGF-A, and capillarization levels in skeletal muscles from obese Zucker diabetic fatty rats compared with those in healthy animals. Our results define Mdm2 as a crucial regulator of capillary maintenance and exercise-induced angiogenesis in skeletal muscle. PMID:22835827

Roudier, Emilie; Forn, Paul; Perry, Mary Ellen; Birot, Olivier

2012-11-01

361

The glucocorticoid system is required for the voluntary exercise-induced enhancement of learning and memory in rats.  

PubMed

Although it is well established that voluntary exercise can improve cognitive functions, the underlying mechanisms are largely unknown. Glucocorticoids play an important role in learning and memory functions. This study addressed whether the glucocorticoid system would play a role in the exercise-induced enhancement of learning and memory. Intact rats or those that were either adrenalectomized or daily given the corticosterone-synthesis inhibitor metyrapone were allowed to freely exercise in a running wheel for 10 days. Control animals were kept sedentary for this period. After this period, they were trained and tested on a water-maze spatial task using three-trial per day for 5 consecutive days, succeeded by a probe trial two days later. Exercise increased plasma corticosterone levels, as assessed after this 10-day period. Both adrenalectomy and metyrapone slightly reduced running-wheel activity. Adrenalectomy reduced the plasma corticosterone levels to almost zero whereas metyrapone selectively blocked the exercise-induced increase in corticosterone levels. Exercise significantly improved performance during both training and retention of the water-maze task whereas this effect was absent in both adrenalectomized and metyrapone-treated rats. These findings indicate that the glucocorticoid system play a crucial role in the beneficial effects of voluntary exercise on cognitive functions in rats. PMID:21147170

Hajisoltani, Razieh; Rashidy-Pour, Ali; Vafaei, Abbas A; Ghaderdoost, Behshid; Bandegi, Ahmad Reza; Motamedi, Fereshteh

2011-05-16

362

Mitochondrial protein turnover: methods to measure turnover rates on a large scale.  

PubMed

Mitochondrial proteins carry out diverse cellular functions including ATP synthesis, ion homeostasis, cell death signaling, and fatty acid metabolism and biogenesis. Compromised mitochondrial quality control is implicated in various human disorders including cardiac diseases. Recently it has emerged that mitochondrial protein turnover can serve as an informative cellular parameter to characterize mitochondrial quality and uncover disease mechanisms. The turnover rate of a mitochondrial protein reflects its homeostasis and dynamics under the quality control systems acting on mitochondria at a particular cell state. This review article summarizes some recent advances and outstanding challenges for measuring the turnover rates of mitochondrial proteins in health and disease. This article is part of a Special Issue entitled "Mitochondria: From Basic Mitochondrial Biology to Cardiovascular Disease". PMID:25451168

Chan, X'avia C Y; Black, Caitlin M; Lin, Amanda J; Ping, Peipei; Lau, Edward

2015-01-01

363

Application of cytoplasmic Ca2+ fluorescence imaging techniques to study the molecular mechanisms of exercise-induced fatigue eliminated by Chinese medicine ginseng extract  

NASA Astrophysics Data System (ADS)

The exercise-induced fatigue eliminated by Chinese medicine offers advantages including good efficiency and smaller side-effects, however, the exact mechanisms have not been classified. A lot of literatures indicated the cytosolic free Ca2+ concentrations of skeletal muscle cells increased significantly during exercise-induced fatigue. This study is aimed to establish a rat skeletal muscle cell model of exercise-induced fatigue. We applied cytoplasmic Ca2+ fluorescence imaging techniques to study the molecular mechanisms of exercise-induced fatigue eliminated by Chinese medicine ginseng extract. In our research, the muscle tissues from the newborn 3 days rats were taken out and digested into cells. The cells were randomly divided into the ginseng extract group and the control group. The cells from the two groups were cultured in the medium respectively added 2mg/ml ginseng extract and 2mg/ml D-hanks solution. After differentiating into myotubes, the two groups of cells treated with a fluorescent probe Fluo-3 AM were put on the confocal microscope and the fluorescence intensity of cells pre- and post- stimulation with dexamethasone were detected. It was found that cytoplasmic Ca2+ concentrations of the two groups of cells both increased post-stimulation, however, the increasing amplitude of fluorescence intensity of the ginseng extract group was significantly lower than that of the control group. In conclusion, stimulating the cells with dexamethasone is a kind of workable cell models of exercise-induced fatigue, and the molecular mechanisms of exercise-induced fatigue eliminated by ginseng extract may be connected to regulatating cytosolic free Ca2+ concentrations.

Liu, Yi; Zhao, Yanping; Zhang, Heming; Liu, Songhao

2009-11-01

364

Mitochondrial loss, dysfunction and altered dynamics in Huntington's disease  

PubMed Central

Although a direct causative pathway from the gene mutation to the selective neostriatal neurodegeneration remains unclear in Huntington's disease (HD), one putative pathological mechanism reported to play a prominent role in the pathogenesis of this neurological disorder is mitochondrial dysfunction. We examined mitochondria in preferentially vulnerable striatal calbindin-positive neurons in moderate-to-severe grade HD patients, using antisera against mitochondrial markers of COX2, SOD2 and cytochrome c. Combined calbindin and mitochondrial marker immunofluorescence showed a significant and progressive grade-dependent reduction in the number of mitochondria in spiny striatal neurons, with marked alteration in size. Consistent with mitochondrial loss, there was a reduction in COX2 protein levels using western analysis that corresponded with disease severity. In addition, both mitochondrial transcription factor A, a regulator of mtDNA, and peroxisome proliferator-activated receptor-co-activator gamma-1 alpha, a key transcriptional regulator of energy metabolism and mitochondrial biogenesis, were also significantly reduced with increasing disease severity. Abnormalities in mitochondrial dynamics were observed, showing a significant increase in the fission protein Drp1 and a reduction in the expression of the fusion protein mitofusin 1. Lastly, mitochondrial PCR array profiling in HD caudate nucleus specimens showed increased mRNA expression of proteins involved in mitochondrial localization, membrane translocation and polarization and transport that paralleled mitochondrial derangement. These findings reveal that there are both mitochondrial loss and altered mitochondrial morphogenesis with increased mitochondrial fission and reduced fusion in HD. These findings provide further evidence that mitochondrial dysfunction plays a critical role in the pathogenesis of HD. PMID:20660112

Kim, Jinho; Moody, Jennifer P.; Edgerly, Christina K.; Bordiuk, Olivia L.; Cormier, Kerry; Smith, Karen; Beal, M. Flint; Ferrante, Robert J.

2010-01-01

365

Effective treatment of mitochondrial myopathy by nicotinamide riboside, a vitamin B3  

PubMed Central

Nutrient availability is the major regulator of life and reproduction, and a complex cellular signaling network has evolved to adapt organisms to fasting. These sensor pathways monitor cellular energy metabolism, especially mitochondrial ATP production and NAD+/NADH ratio, as major signals for nutritional state. We hypothesized that these signals would be modified by mitochondrial respiratory chain disease, because of inefficient NADH utilization and ATP production. Oral administration of nicotinamide riboside (NR), a vitamin B3 and NAD+ precursor, was previously shown to boost NAD+ levels in mice and to induce mitochondrial biogenesis. Here, we treated mitochondrial myopathy mice with NR. This vitamin effectively delayed early- and late-stage disease progression, by robustly inducing mitochondrial biogenesis in skeletal muscle and brown adipose tissue, preventing mitochondrial ultrastructure abnormalities and mtDNA deletion formation. NR further stimulated mitochondrial unfolded protein response, suggesting its protective role in mitochondrial disease. These results indicate that NR and strategies boosting NAD+ levels are a promising treatment strategy for mitochondrial myopathy. PMID:24711540

Khan, Nahid A; Auranen, Mari; Paetau, Ilse; Pirinen, Eija; Euro, Liliya; Forsström, Saara; Pasila, Lotta; Velagapudi, Vidya; Carroll, Christopher J; Auwerx, Johan; Suomalainen, Anu

2014-01-01

366

Relationship between Sirt1 expression and mitochondrial proteins during conditions of chronic muscle use and disuse.  

PubMed

Sirt1 is a NAD(+)-dependent histone deacetylase that interacts with the regulatory protein of mitochondrial biogenesis PGC-1alpha and is sensitive to metabolic alterations. We assessed whether a strict relationship between the expression of Sirt1, mitochondrial proteins, and PGC-1alpha existed across tissues possessing a wide range of oxidative capabilities, as well as in skeletal muscle subject to chronic use (voluntary wheel running or electrical stimulation for 7 days, 10 Hz; 3 h/day) or disuse (denervation for up to 21 days) in which organelle biogenesis is altered. PGC-1alpha levels were not closely associated with the expression of Sirt1, measured using immunoblotting or via enzymatic deacetylase activity. The mitochondrial protein cytochrome c increased by 70-90% in soleus and plantaris muscles of running animals, whereas Sirt1 activity remained unchanged. In chronically stimulated muscle, cytochrome c was increased by 30% compared with nonstimulated muscle, whereas Sirt1 activity was increased modestly by 20-25%. In contrast, in denervated muscle, these markers of mitochondrial content were decreased by 30-50% compared with the control muscle, whereas Sirt1 activity was increased by 75-80%. Our data suggest that Sirt1 and PGC-1alpha expression are independently regulated and that, although Sirt1 activity may be involved in mitochondrial biogenesis, its expression is not closely correlated to changes in mitochondrial proteins during conditions of chronic muscle use and disuse. PMID:19797682

Chabi, Beatrice; Adhihetty, Peter J; O'Leary, Michael F N; Menzies, Keir J; Hood, David A

2009-12-01

367

Transcriptional Regulation of Insulin-degrading Enzyme Modulates Mitochondrial Amyloid ? (A?) Peptide Catabolism and Functionality*  

PubMed Central

Studies of post-mortem brains from Alzheimer disease patients suggest that oxidative damage induced by mitochondrial amyloid ? (mitA?) accumulation is associated with mitochondrial dysfunction. However, the regulation of mitA? metabolism is unknown. One of the proteases involved in mitA? catabolism is the long insulin-degrading enzyme (IDE) isoform (IDE-Met1). However, the mechanisms of its expression are unknown, and its presence in brain is uncertain. We detected IDE-Met1 in brain and showed that its expression is regulated by the mitochondrial biogenesis pathway (PGC-1?/NRF-1). A strong positive correlation between PGC-1? or NRF-1 and long IDE isoform transcripts was found in non-demented brains. This correlation was weaker in Alzheimer disease. In vitro inhibition of IDE increased mitA? and impaired mitochondrial respiration. These changes were restored by inhibition of ?-secretase or promotion of mitochondrial biogenesis. Our results suggest that IDE-Met1 links the mitochondrial biogenesis pathway with mitA? levels and organelle functionality. PMID:23525105

Leal, María C.; Magnani, Natalia; Villordo, Sergio; Buslje, Cristina Marino; Evelson, Pablo; Castaño, Eduardo M.; Morelli, Laura

2013-01-01

368

Mitochondrial genetics  

Microsoft Academic Search

1.A series of CS revertants has been selected from various strains (both ?+ and ?-) carrying a CR mitochondrial mutation at the RIB1 locus. The properties of mitochondrial recombination exhibited by these CS revertants in various crosses, have been examined systematically. The ? allele of the CS revertants has been defined in crosses with ?+ and ?- tester strains using

B. Dujon; M. Bolotin-Fukuhara; D. Coen; J. Deutsch; P. Netter; P. P. Slonimski; L. Weill

1976-01-01

369

Mitochondrial function contributes to oxysterol-induced osteogenic differentiation in mouse embryonic stem cells.  

PubMed

Oxysterols, oxidized derivatives of cholesterol, are biologically active molecules. Specific oxysterols have potent osteogenic properties that act on osteoprogenitor cells. However, the molecular mechanisms underlying these osteoinductive effects on embryonic stem cells (ESCs) are unknown. This study investigated the effect of an oxysterol combination of 22(S)-hydroxycholesterol and 20(S)-hydroxycholesterol (SS) on osteogenic differentiation of ESCs and the alterations to mitochondrial activity during differentiation. Osteogenic differentiation was assessed by alkaline phosphatase (ALP) activity, matrix mineralization, mRNA expression of osteogenic factors, runt-related transcription factor 2, osterix, and osteocalcin, and protein levels of collagen type IA (COLIA) and osteopontin (OPN). Treatment of cells with SS increased osteoinductive activity compared to the control group. Intracellular reactive oxygen species production, intracellular ATP content, mitochondrial membrane potential, mitochondrial mass, mitochondrial DNA copy number, and mRNA expression of peroxisome proliferator-activated receptor-? coactivators 1? and ?, transcription factors involved in mitochondrial biogenesis, were significantly increased during osteogenesis, indicating upregulation of mitochondrial activity. Oxysterol combinations also increased protein levels of mitochondrial respiratory complexes I-V. We also found that SS treatment increased hedgehog signaling target genes, Smo and Gli1 expression. Inhibition of Hh signaling by cyclopamine suppressed mitochondrial biogenesis and ESC osteogenesis. Subsequently, oxysterol-induced Wnt/?-catenin pathways were inhibited by repression of Hh signaling and mitochondrial biogenesis. Transfection of ?-catenin specific siRNA decreased the protein levels of COLIA and OPN, as well as ALP activity. Collectively, these data suggest that lipid-based oxysterols enhance differentiation of ESCs toward the osteogenic lineage by regulating mitochondrial activity, canonical Hh/Gli, and Wnt/?-catenin signaling. PMID:25523141

Kwon, Il Keun; Lee, Sang Cheon; Hwang, Yu-Shik; Heo, Jung Sun

2015-03-01

370

The role of nutritional supplements in the prevention and treatment of resistance exercise-induced skeletal muscle injury.  

PubMed

The topic of exercise-induced skeletal muscle injury has received considerable attention in recent years. Likewise, strategies to minimise the injury resulting from heavy resistance exercise have been studied. Over the past 15 years, several investigations have been performed focused on the role of nutritional supplements to attenuate signs and symptoms of muscle injury. Of these, some have reported favourable results, while many others have reported no benefit of the selected nutrient. Despite these mixed findings, recommendations for the use of nutritional supplements for the purposes of attenuating muscle injury are rampant within the popular fitness media and athletic world, largely without scientific support. Those nutrients include the antioxidant vitamin C (ascorbic acid) and vitamin E (tocopherol), N-acetyl-cysteine, flavonoids, L-carnitine, astaxanthin, beta-hydroxy-beta-methylbutyrate, creatine monohydrate, essential fatty acids, branched-chain amino acids, bromelain, proteins and carbohydrates. A discussion of all published peer-reviewed articles in reference to these nutrients and their impact on resistance exercise-induced skeletal muscle injury is presented, in addition to a brief view into the potential mechanism of action for each nutrient.Based on the current state of knowledge, the following conclusions can be made with regard to nutritional supplements and their role in attenuating signs and symptoms of skeletal muscle injury occurring as a consequence of heavy resistance exercise: (i) there appears to be a potential role for certain supplements (vitamin C, vitamin E, flavonoids, and L-carnitine); (ii) these supplements cannot effectively eliminate muscle injury, only attenuate certain signs and symptoms; (iii) it is presently unclear what the optimal dosage of these nutrients is (whether used alone or in combination); (iv) it is unclear what the optimal pretreatment period is; and (v) the effectiveness is largely specific to non-resistance trained individuals.Ultimately, because so few studies have been conducted in this area, it is difficult to recommend with confidence the use of selected nutrients for the sole purpose of minimising signs and symptoms of resistance exercise-induced muscle injury, in particular with regard to resistance-trained individuals. PMID:17503877

Bloomer, Richard J

2007-01-01

371

PI(5)P Regulates Autophagosome Biogenesis  

PubMed Central

Summary Phosphatidylinositol 3-phosphate (PI(3)P), the product of class III PI3K VPS34, recruits specific autophagic effectors, like WIPI2, during the initial steps of autophagosome biogenesis and thereby regulates canonical autophagy. However, mammalian cells can produce autophagosomes through enigmatic noncanonical VPS34-independent pathways. Here we show that PI(5)P can regulate autophagy via PI(3)P effectors and thereby identify a mechanistic explanation for forms of noncanonical autophagy. PI(5)P synthesis by the phosphatidylinositol 5-kinase PIKfyve was required for autophagosome biogenesis, and it increased levels of PI(5)P, stimulated autophagy, and reduced the levels of autophagic substrates. Inactivation of VPS34 impaired recruitment of WIPI2 and DFCP1 to autophagic precursors, reduced ATG5-ATG12 conjugation, and compromised autophagosome formation. However, these phenotypes were rescued by PI(5)P in VPS34-inactivated cells. These findings provide a mechanistic framework for alternative VPS34-independent autophagy-initiating pathways, like glucose starvation, and unravel a cytoplasmic function for PI(5)P, which previously has been linked predominantly to nuclear roles. PMID:25578879

Vicinanza, Mariella; Korolchuk, Viktor I.; Ashkenazi, Avraham; Puri, Claudia; Menzies, Fiona M.; Clarke, Jonathan H.; Rubinsztein, David C.

2015-01-01

372

MicroRNA biogenesis: Regulating the Regulators  

PubMed Central

MicroRNAs (miRNAs) function as 21–24 nucleotide guide RNAs that use partial base-pairing to recognize target messenger RNAs and repress their expression. As a large fraction of protein-coding genes are under miRNA control, production of the appropriate level of specific miRNAs at the right time and in the right place is integral to most gene regulatory pathways. MiRNA biogenesis initiates with transcription, followed by multiple processing steps to produce the mature miRNA. Every step of miRNA production is subject to regulation and disruption of these control mechanisms has been linked to numerous human diseases, where the balance between the expression of miRNAs and their targets becomes distorted. Here we review the basic steps of miRNA biogenesis and describe the various factors that control miRNA transcription, processing and stability in animal cells. The tremendous effort put into producing the appropriate type and level of specific miRNAs underscores the critical role of these small RNAs in gene regulation. PMID:23163351

Finnegan, Emily F.; Pasquinelli, Amy E.

2012-01-01

373

[2Fe-2S] cluster transfer in iron-sulfur protein biogenesis.  

PubMed

Monothiol glutaredoxins play a crucial role in iron-sulfur (Fe/S) protein biogenesis. Essentially all of them can coordinate a [2Fe-2S] cluster and have been proposed to mediate the transfer of [2Fe-2S] clusters from scaffold proteins to target apo proteins, possibly by acting as cluster transfer proteins. The molecular basis of [2Fe-2S] cluster transfer from monothiol glutaredoxins to target proteins is a fundamental, but still unresolved, aspect to be defined in Fe/S protein biogenesis. In mitochondria monothiol glutaredoxin 5 (GRX5) is involved in the maturation of all cellular Fe/S proteins and participates in cellular iron regulation. Here we show that the structural plasticity of the dimeric state of the [2Fe-2S] bound form of human GRX5 (holo hGRX5) is the crucial factor that allows an efficient cluster transfer to the partner proteins human ISCA1 and ISCA2 by a specific protein-protein recognition mechanism. Holo hGRX5 works as a metallochaperone preventing the [2Fe-2S] cluster to be released in solution in the presence of physiological concentrations of glutathione and forming a transient, cluster-mediated protein-protein intermediate with two physiological protein partners receiving the [2Fe-2S] cluster. The cluster transfer mechanism defined here may extend to other mitochondrial [2Fe-2S] target proteins. PMID:24733926

Banci, Lucia; Brancaccio, Diego; Ciofi-Baffoni, Simone; Del Conte, Rebecca; Gadepalli, Ravisekhar; Mikolajczyk, Maciej; Neri, Sara; Piccioli, Mario; Winkelmann, Julia

2014-04-29

374

Biogenesis of cbb(3)-type cytochrome c oxidase in Rhodobacter capsulatus.  

PubMed

The cbb(3)-type cytochrome c oxidases (cbb(3)-Cox) constitute the second most abundant cytochrome c oxidase (Cox) group after the mitochondrial-like aa(3)-type Cox. They are present in bacteria only, and are considered to represent a primordial innovation in the domain of Eubacteria due to their phylogenetic distribution and their similarity to nitric oxide (NO) reductases. They are crucial for the onset of many anaerobic biological processes, such as anoxygenic photosynthesis or nitrogen fixation. In addition, they are prevalent in many pathogenic bacteria, and important for colonizing low oxygen tissues. Studies related to cbb(3)-Cox provide a fascinating paradigm for the biogenesis of sophisticated oligomeric membrane proteins. Complex subunit maturation and assembly machineries, producing the c-type cytochromes and the binuclear heme b(3)-Cu(B) center, have to be coordinated precisely both temporally and spatially to yield a functional cbb(3)-Cox enzyme. In this review we summarize our current knowledge on the structure, regulation and assembly of cbb(3)-Cox, and provide a highly tentative model for cbb(3)-Cox assembly and formation of its heme b(3)-Cu(B) binuclear center. This article is part of a Special Issue entitled: Biogenesis/Assembly of Respiratory Enzyme Complexes. PMID:22079199

Ekici, Seda; Pawlik, Grzegorz; Lohmeyer, Eva; Koch, Hans-Georg; Daldal, Fevzi

2012-06-01

375

Modulation of mitochondrial capacity and angiogenesis by red wine polyphenols via estrogen receptor, NADPH oxidase and nitric oxide synthase pathways.  

PubMed

Red wine polyphenolic compounds (RWPC) are reported to exert vasculoprotective properties on endothelial cells, involving nitric oxide (NO) release via a redox-sensitive pathway. This NO release involves the activation of the estrogen receptor-alpha (ER?). Paradoxical effects of a RWPC treatment occur in a rat model of post-ischemic neovascularization, where a low-dose is pro-angiogenic while a higher dose is anti-angiogenic. NO and ER? are key regulators of mitochondrial capacity, and angiogenesis is a highly energetic process associated with mitochondrial biogenesis. However, whether RWPC induces changes in mitochondrial capacity has never been addressed. We investigated the effects of RWPC at low (10(-4)g/l, LCP) and high concentration (10(-2)g/l, HCP) in human endothelial cells. Mitochondrial respiration, expression of mitochondrial biogenesis factors and mitochondrial DNA content were assessed using oxygraphy and quantitative PCR respectively. In vitro capillary formation using ECM gel(®) was also performed. Treatment with LCP increased mitochondrial respiration, with a maximal effect achieved at 48h. LCP also increased expression of several mitochondrial biogenesis factors and mitochondrial DNA content. In contrast, HCP did not affect these parameters. Furthermore, LCP modulated both mitochondrial capacity and angiogenesis through mechanisms sensitive to ER, NADPH oxidase and NO-synthase inhibitors. Finally, the inhibition of mitochondrial protein synthesis abolished the pro-angiogenic capacity of LCP. These results suggest a possible association between the modulation of mitochondrial capacity by LCP and its pro-angiogenic activity. These data provide evidence for a role of mitochondria in the regulation of angiogenesis by RWPC. PMID:23333619

Duluc, Lucie; Jacques, Caroline; Soleti, Raffaella; Iacobazzi, Francesco; Simard, Gilles; Andriantsitohaina, Ramaroson

2013-04-01

376

Concentration-effect relationship of l-propranolol and metoprolol in spontaneous hypertensive rats after exercise-induced tachycardia.  

PubMed

The concentration-effect relationship of l-propranolol and dl-metoprolol were investigated in spontaneous hypertensive rats using reduction in exercise-induced tachycardia as a pharmacodynamic endpoint. The influence of protein binding on the effect relationship was also assessed. The rats were assigned to treatment or placebo groups, where each group received three randomly selected consecutively increasing steady-state infusions. Different pharmacodynamic effect models were fitted to the data, using nonlinear mixed effect modeling. The data were best described by a combined effect model, with a sum of an ordinary Imax and a linear model. At the lower concentration range, the ordinary Imax model dominated, although at higher concentrations, the effect was linearly related to the antagonist concentration. The Imax were 83 +/- 6 and 103 +/- 6 beats . min-1 and the IC50 were 18.1 +/- 4.3 and 50.6 +/- 15.2 ng/ml for l-propranolol and dl-metoprolol, respectively. The slope in the linear model was steeper for l-propranolol than for dl-metoprolol, 28.9 +/- 2.8 and 4.48 +/- 0.39 beats . ml . (min . microgram)-1, respectively. Plasma protein binding of l-propranolol was saturable. The unbound IC50 for l-propranolol was 1.14 +/- 0.27 ng/ml. The concentration-effect relationship of l-propranolol was altered at higher plasma concentrations, due to saturable protein binding. The Imax and the linear concentration-effect relationship may be interpreted as a specific beta-antagonist effect and a membrane-stabilizing effect, respectively. Using exercise-induced tachycardia as a pharmacodynamic endpoint, to study the effect of beta-antagonists in spontaneous hypertensive rats, seems to give reliable results and can be a useful model to extrapolate to humans. PMID:9732372

Brynne, L; Karlsson, M O; Paalzow, L K

1998-09-01

377

Exercise-induced QRS amplitude changes in patients with isolated myocardial bridging: a marker of myocardial ischemia.  

PubMed

Myocardial bridging (MB) of coronary arteries has been considered as an incidental angio-graphic finding; however, several reports suggest its association with angina pectoris, myocardial ischemia, and even infarction. In this study the authors aimed to assess exercise-induced QRS changes in patients with isolated MB and to compare those with coronary artery disease (CAD) and healthy subjects. The study population consisted of 17 patients with angiographically proven MB (group 1), 16 patients with left anterior descending (LAD) artery stenosis (group 2), and 14 healthy subjects (group 3). Each subject underwent treadmill exercise testing according to Bruce protocol. In each subject amplitude of the Q, R, and S waves in leads aVF and V(5) was measured manually before and immediately after exercise. The Athens QRS score was calculated by subtracting the Q-, R-, and S-wave differences in leads aVF and V(5). Baseline characteristics of each group were similar. There was no difference among the groups with respect to exercise testing parameters (peak heart rate, blood pressure, test duration, etc). In group 1, ST-segment depression ratio was found to be higher than that of group 3 but lower than that of group 2. In group 1, exercise QRS score was found to be lower than that of group 3 while it was higher than that of group 2 (2.9 +/- 2.3 vs 6.5 +/- 3.2 p = 0.001 and 2.9 +/- 2.3 vs 2.6 +/- 2.4 p = 0.001, respectively). In patients with MB exercise, QRS score was significantly lower than in those with normal coronary flow while it was higher in those with CAD. This may result from exercise-induced ischemia at the area perfused by the bridged artery. PMID:15889193

Turkmen, Muhsin; Barutcu, Irfan; Esen, Ali Metin; Karakaya, Osman; Esen, Ozlem; Basaran, Yelda

2005-01-01

378

Protective effect of epimedium combined with oligomeric proanthocyanidins on exercise-induced renal ischemia-reperfusion injury of rats  

PubMed Central

Objective: This paper studied the protective effect and mechanism of epimedium combined with oligomeric proanthocyanidins on exercise-induced renal ischemia-reperfusion injury of rats. Methods: In the experiment, the rats were given exhaustive swimming training and then their blood urea nitrogen (BUN) and other biochemical indexes were measured after they were given gastric perfusion with 6.01 g/kg doze of epimedium and 50 mg/kg doze of oligomeric proanthocyanidins for 56 days. Results: The result indicated that 8 weeks of over training led to ischemia-reperfusion injury of rats. Moreover, their kidney tissues were significantly changed pathologically and renal functions drastically damaged. BUN and serum creatinine increased and EOM group (P < 0.05), OPCOM group (P < 0.05) and EOPCOM group (P < 0.01) were lower than OM group. EOPCOM group was lower than OPCOM group. SOD activity decreased, EOM group (P < 0.05), OPCOM group (P < 0.05), EOPCOM group (P < 0.01) higher than OM group, and EOPCOM group (P < 0.05) higher than OPCOM group. The content of MDA increased, EOM group (P < 0.05), OPCOM group (P < 0.05), EOPCOM group (P < 0.01) lower than OM group, and EOPCOM group (P < 0.05) lower than OPCOM group. Conclusion: Both epimedium and oligomeric proanthocyanidins can boost SOD activity, clean oxygen radicals, clean and alleviate peroxidation of lipids, which exert protection on exercise-induced renal ischemia-reperfusion. The two combined yield a much better result.

Zhang, Hua; Sun, Xiao-Qin; Cao, Jian-Min; Zhou, Hai-Tao; Guo, Xian; Wang, Yi

2014-01-01

379

Prevalence and prognostic significance of exercise-induced silent myocardial ischemia detected by thallium scintigraphy and electrocardiography in asymptomatic volunteers  

SciTech Connect

Although a silent ischemic electrocardiographic response to treadmill exercise in clinically healthy populations is associated with an increased likelihood of future coronary events (i.e., angina pectoris, myocardial infarction, or cardiac death), such a response has a low predictive value for future events because of the low prevalence of disease in asymptomatic populations. To examine whether detection of reduced regional perfusion by thallium scintigraphy improved the predictive value of exercise-induced ST segment depression, we performed maximal treadmill exercise electrocardiography (ECG) and thallium scintigraphy (201Tl) in 407 asymptomatic volunteers 40-96 years of age (mean = 60) from the Baltimore Longitudinal Study on Aging. The prevalence of exercise-induced silent ischemia, defined by concordant ST segment depression and a thallium perfusion defect, increased more than sevenfold from 2% in the fifth and sixth decades to 15% in the ninth decade. Over a mean follow-up period of 4.6 years, cardiac events developed in 9.8% of subjects and consisted of 20 cases of new angina pectoris, 13 myocardial infarctions, and seven deaths. Events occurred in 7% of individuals with both negative 201Tl and ECG, 8% of those with either test positive, and 48% of those in whom both tests were positive (p less than 0.001). By proportional hazards analysis, age, hypertension, exercise duration, and a concordant positive ECG and 201Tl result were independent predictors of coronary events. Furthermore, those with positive ECG and 201Tl had a 3.6-fold relative risk for subsequent coronary events, independent of conventional risk factors.

Fleg, J.L.; Gerstenblith, G.; Zonderman, A.B.; Becker, L.C.; Weisfeldt, M.L.; Costa, P.T. Jr.; Lakatta, E.G. (National Institute on Aging, Baltimore, MD (USA))

1990-02-01

380

Efficacy of whey protein supplementation on resistance exercise-induced changes in muscle strength, lean mass, and function in mobility-limited older adults  

Technology Transfer Automated Retrieval System (TEKTRAN)

Whey protein supplementation may augment resistance exercise-induced increases in muscle strength and mass. Further studies are required to determine whether this effect extends to functionally compromised older adults. The objectives of the study were to compare the effects of whey protein concent...

381

Double-blind, placebo-controlled study of single doses of chlorofluorocarbon (CFC) and CFC-Free cromolyn sodium for exercise-induced bronchoconstriction  

Microsoft Academic Search

The objective of this study was to compare the protective effects of a single dose of either cromolyn sodium containing chlorofluorocarbon (CFC) as a propellant or CFC-free cromolyn sodium containing hydrofluoroalkane (HFA) as a propellant with those of placebo. Seventeen patients with documented exercise-induced bronchoconstriction received a single dose of each of the 2 formulations and placebo with washout periods

William Storms

1999-01-01

382

Reduction in Obesity and Related Comorbid Conditions after Diet-Induced Weight Loss or Exercise-Induced Weight Loss in Men A Randomized, Controlled Trial  

Microsoft Academic Search

Background: The independent effects of diet- or exercise-induced weight loss on the reduction of obesity and related comorbid conditions are not known. The effects of exercise without weight loss on fat distribution and other risk factors are also unclear. Objective: To determine the effects of equivalent diet- or exer- cise-induced weight loss and exercise without weight loss on subcutaneous fat,

Robert Ross; Damon Dagnone; Peter J. H. Jones; Heidi Smith; Anne Paddags; Robert Hudson; Ian Janssen

383

Chromium picolinate and conjugated linoleic acid do not synergistically influence diet- and exercise-induced changes in body composition and health indexes in overweight women  

Technology Transfer Automated Retrieval System (TEKTRAN)

Objective: This study assessed the effects of combined chromium picolinate (CP) and conjugated linoleic acid (CLA) supplementation on energy-restriction and exercise-induced changes in body composition, glucose metabolism, lipid-lipoprotein profile, and blood pressure in overweight, pre-menopausal w...

384

Insulin Granule Biogenesis, Trafficking and Exocytosis  

PubMed Central

It is becoming increasingly apparent that beta cell dysfunction resulting in abnormal insulin secretion is the essential element in the progression of patients from a state of impaired glucose tolerance to frank type 2 diabetes (Del Prato, 2003; Del Prato and Tiengo, 2001). Although extensive studies have examined the molecular, cellular and physiologic mechanisms of insulin granule biogenesis, sorting, and exocytosis the precise mechanisms controlling these processes and their dysregulation in the developed of diabetes remains an area of important investigation. We now know that insulin biogenesis initiates with the synthesis of preproinsulin in rough endoplastic reticulum and conversion of preproinsulin to proinsulin. Proinsulin begins to be packaged in the Trans-Golgi Network and is sorting into immature secretory granules. These immature granules become acidic via ATP-dependent proton pump and proinsulin undergoes proteolytic cleavage resulting the formation of insulin and C-peptide. During the granule maturation process, insulin is crystallized with zinc and calcium in the form of dense-core granules and unwanted cargo and membrane proteins undergo selective retrograde trafficking to either the constitutive trafficking pathway for secretion or to degradative pathways. The newly formed mature dense-core insulin granules populate two different intracellular pools, the readily releasable pools (RRP) and the reserved pool. These two distinct populations are thought to be responsible for the biphasic nature of insulin release in which the RRP granules are associated with the plasma membrane and undergo an acute calcium-dependent release accounting for first phase insulin secretion. In contrast, second phase insulin secretion requires the trafficking of the reserved granule pool to the plasma membrane. The initial trigger for insulin granule fusion with the plasma membrane is a rise in intracellular calcium and in the case of glucose stimulation results from increased production of ATP, closure of the ATP-sensitive potassium channel and cellular depolarization. In turn, this opens voltage-dependent calcium channels allowing increased influx of extracellular calcium. Calcium is thought to bind to members of the fusion regulatory proteins synaptogamin that functionally repressors the fusion inhibitory protein complexin. Both complexin and synaptogamin interact as well as several other regulatory proteins interact with the core fusion machinery composed of the Q- or t-SNARE proteins syntaxin 1 and SNAP25 in the plasmamembrane that assembles with the R- or v-SNARE protein VAMP2 in insulin granules. In this chapter we will review the current progress of insulin granule biogenesis, sorting, trafficking, exocytosis and signaling pathways that comprise the molecular basis of glucose-dependent insulin secretion. PMID:19251047

Hou, June Chunqiu; Min, Le; Pessin, Jeffrey E.

2015-01-01

385

Effects of levosimendan on mitochondrial function in patients with septic shock: a randomized trial.  

PubMed

Mitochondrial dysfunction is key feature of septic shock and contributes to the development of sepsis related organ dysfunction. It is characterized by a variable reduction of the respiratory chain (RC) activities, altered mitochondrial morphology and reactive oxygen species production. Recent data have reported the efficacy of levosimendan, a calcium sensitizer, in improving heart performance and organ perfusion in critically ill patients. Moreover, it has been demonstrated that Levosimendan has antioxidant properties. Nevertheless, the effects of levosimendan on mitochondrial function are not fully elucidated. The objective of this study was therefore to evaluate the effect of levosimendan on mitochondria performance. Five mitochondrial parameters were screened: the redox status; the amount of scavenging enzymes; the activities of the RC complexes; the mitochondrial content; the steady state levels of the RC subunits; the mitochondrial biogenesis. Our results show that patients treated with levosimendan had a significant reduction of glutathionylated proteins and an increase in the amount of the antioxidant enzyme MnSOD, underlining its antioxidant properties. The activities of the RC complexes I, II and III were unchanged in the mitochondria of patients treated with levosimendan compared to controls whereas the mitochondrial content was significantly higher in levosimendan vs. control patients. Finally, evaluation of mitochondrial biogenesis did not show any significant difference in the two groups, although an overall increase in the amount of the RC subunits was observed in the levosimendan group. In conclusion, our study demonstrated that in septic shock patients, Levosimendan exerts antioxidant action by increasing antioxidant defense and lowering oxidative damage. PMID:24657218

Torraco, Alessandra; Carrozzo, Rosalba; Piemonte, Fiorella; Pastore, Anna; Tozzi, Giulia; Verrigni, Daniela; Assenza, Marco; Orecchioni, Alessandra; D'Egidio, Annalia; Marraffa, Elisa; Landoni, Giovanni; Bertini, Enrico; Morelli, Andrea

2014-07-01

386

Exercise-Induced Oxidative Stress: Cellular Mechanisms and Impact on Muscle Force Production  

PubMed Central

The first suggestion that physical exercise results in free radical-mediated damage to tissues appeared in 1978, and the past three decades have resulted in a large growth of knowledge regarding exercise and oxidative stress. Although the sources of oxidant production during exercise continue to be debated, it is now well established that both resting and contracting skeletal muscles produce reactive oxygen species and reactive nitrogen species. Importantly, intense and prolonged exercise can result in oxidative damage to both proteins and lipids in the contracting myocytes. Furthermore, oxidants can modulate a number of cell signaling pathways and regulate the expression of multiple genes in eukaryotic cells. This oxidant-mediated change in gene expression involves changes at transcriptional, mRNA stability, and signal transduction levels. Furthermore, numerous products associated with oxidant-modulated genes have been identified and include antioxidant enzymes, stress proteins, DNA repair proteins, and mitochondrial electron transport proteins. Interestingly, low and physiological levels of reactive oxygen species are required for normal force production in skeletal muscle, but high levels of reactive oxygen species promote contractile dysfunction resulting in muscle weakness and fatigue. Ongoing research continues to probe the mechanisms by which oxidants influence skeletal muscle contractile properties and to explore interventions capable of protecting muscle from oxidant-mediated dysfunction. PMID:18923182

POWERS, SCOTT K.; JACKSON, MALCOLM J.

2010-01-01

387

Prevalence and prognostic significance of exercise-induced non-sustained ventricular tachycardia in asymptomatic volunteers: The Baltimore Longitudinal Study of Aging  

PubMed Central

Objectives To determine the clinical predictors and prognostic significance of exercise-induced non-sustained ventricular tachycardia (NSVT) in a large population of asymptomatic volunteers. Background Prior studies report variable risk associated with exercise-induced ventricular arrhythmia. Methods Subjects in the Baltimore Longitudinal Study of Aging free of known cardiovascular (CV) disease who completed at least one symptom-limited exercise treadmill test between 1977 and 2001 were included. NSVT episodes were characterized by QRS morphology, duration, and rate. Subjects underwent follow-up clinical evaluation every two years. Results The 2099 subjects (mean age 52.0 yrs, 52.2% male) underwent a mean of 2.7 exercise tests, on which 79 (3.7%) developed NSVT with exercise on at least 1 test. The NSVT had median duration of 3 beats (?5 beats in 84%), and median rate of 175 bpm. Subjects with (vs. without) NSVT were older (67±12 yr vs. 51±17 yr, p < 0.0001), and more likely to be male (80% vs 51%, p< 0.0001), and to have baseline ECG abnormalities (50% vs. 17%, p<0.0001) or ischemic ST segment changes with exercise (20% vs 10%, p=0.004). Over a mean follow-up of 13.5 ± 7.7 yrs, 518 deaths (24.6%) occurred. After multivariable adjustment for age, sex, and coronary risk factors, exercise-induced NSVT was not significantly associated with total mortality (HR=1.30 [95% CI 0.89–1.90], p=0.17). Conclusions Exercise-induced NSVT occurred in nearly 4% of this asymptomatic adult cohort. This finding increased with age and was more common in men. After adjustment for clinical variables, exercise-induced NSVT did not independently increase risk of total mortality. PMID:23747767

Marine, Joseph E.; Shetty, Veena; Chow, Grant V.; Wright, Jeanette; Gerstenblith, Gary; Najjar, Samer S.; Lakatta, Edward G.; Fleg, Jerome L.

2013-01-01

388

Biogenesis of respiratory cytochromes in bacteria.  

PubMed Central

Biogenesis of respiratory cytochromes is defined as consisting of the posttranslational processes that are necessary to assemble apoprotein, heme, and sometimes additional cofactors into mature enzyme complexes with electron transfer functions. Different biochemical reactions take place during maturation: (i) targeting of the apoprotein to or through the cytoplasmic membrane to its subcellular destination; (ii) proteolytic processing of precursor forms; (iii) assembly of subunits in the membrane and oligomerization; (iv) translocation and/or modification of heme and covalent or noncovalent binding to the protein moiety; (v) transport, processing, and incorporation of other cofactors; and (vi) folding and stabilization of the protein. These steps are discussed for the maturation of different oxidoreductase complexes, and they are arranged in a linear pathway to best account for experimental findings from studies concerning cytochrome biogenesis. The example of the best-studied case, i.e., maturation of cytochrome c, appears to consist of a pathway that requires at least nine specific genes and more general cellular functions such as protein secretion or the control of the redox state in the periplasm. Covalent attachment of heme appears to be enzyme catalyzed and takes place in the periplasm after translocation of the precursor through the membrane. The genetic characterization and the putative biochemical functions of cytochrome c-specific maturation proteins suggest that they may be organized in a membrane-bound maturase complex. Formation of the multisubunit cytochrome bc, complex and several terminal oxidases of the bo3, bd, aa3, and cbb3 types is discussed in detail, and models for linear maturation pathways are proposed wherever possible. PMID:9293186

Thöny-Meyer, L

1997-01-01

389

Iron regulatory protein 1 sustains mitochondrial iron loading and function in frataxin deficiency.  

PubMed

Mitochondrial iron accumulation is a hallmark of diseases associated with impaired iron-sulfur cluster (Fe-S) biogenesis, such as Friedreich ataxia linked to frataxin (FXN) deficiency. The pathophysiological relevance of the mitochondrial iron loading and the underlying mechanisms are unknown. Using a mouse model of hepatic FXN deficiency in combination with mice deficient for iron regulatory protein 1 (IRP1), a key regulator of cellular iron metabolism, we show that IRP1 activation in conditions of Fe-S deficiency increases the available cytosolic labile iron pool. Surprisingly, our data indicate that IRP1 activation sustains mitochondrial iron supply and function rather than driving detrimental iron overload. Mitochondrial iron accumulation is shown to depend on mitochondrial dysfunction and heme-dependent upregulation of the mitochondrial iron importer mitoferrin-2. Our results uncover an unexpected protective role of IRP1 in pathological conditions associated with altered Fe-S metabolism. PMID:25651183

Martelli, Alain; Schmucker, Stéphane; Reutenauer, Laurence; Mathieu, Jacques R R; Peyssonnaux, Carole; Karim, Zoubida; Puy, Hervé; Galy, Bruno; Hentze, Matthias W; Puccio, Hélène

2015-02-01

390

IHG-1 Increases Mitochondrial Fusion and Bioenergetic Function.  

PubMed

Induced in high glucose-1 (IHG-1) is a conserved mitochondrial protein associated with diabetic nephropathy (DN) that amplifies profibrotic transforming growth factor (TGF)-?1 signaling and increases mitochondrial biogenesis. Here we report that inhibition of endogenous IHG-1 expression results in reduced mitochondrial respiratory capacity, ATP production, and mitochondrial fusion. Conversely, overexpression of IHG-1 leads to increased mitochondrial fusion and also protects cells from reactive oxygen species-induced apoptosis. IHG-1 forms complexes with known mediators of mitochondrial fusion-mitofusins (Mfns) 1 and 2-and enhances the GTP-binding capacity of Mfn2, suggesting that IHG-1 acts as a guanine nucleotide exchange factor. IHG-1 must be localized to mitochondria to interact with Mfn1 and Mfn2, and this interaction is necessary for increased IHG-1-mediated mitochondrial fusion. Together, these findings indicate that IHG-1 is a novel regulator of both mitochondrial dynamics and bioenergetic function and contributes to cell survival following oxidant stress. We propose that in diabetic kidney disease increased IHG-1 expression protects cell viability and enhances the actions of TGF-?, leading to renal proximal tubule dedifferentiation, an important event in the pathogenesis of this devastating condition. PMID:25008184

Hickey, Fionnuala B; Corcoran, James B; Griffin, Brenda; Bhreathnach, Una; Mortiboys, Heather; Reid, Helen M; Andrews, Darrell; Byrne, Shane; Furlong, Fiona; Martin, Finian; Godson, Catherine; Murphy, Madeline

2014-12-01

391

Molecular basis for an attenuated mitochondrial adaptive plasticity in aged skeletal muscle  

PubMed Central

Our intent was to investigate the mechanisms driving the adaptive potential of subsarcolemmal (SS) and intermyofibrillar (IMF) mitochondria in young (6 mo) and senescent (36 mo) animals in response to a potent stimulus for organelle biogenesis. We employed chronic electrical stimulation (10 Hz, 3 h/day, 7 days) to induce contractile activity of skeletal muscle in 6 and 36 mo F344XBN rats. Subsequent to chronic activity, acute stimulation (1 Hz, 5 min) in situ revealed greater fatigue resistance in both age groups. However, the improvement in endurance was significantly greater in the young, compared to the old animals. Chronic muscle use also augmented SS and IMF mitochondrial volume to a greater extent in young muscle. The molecular basis for the diminished organelle expansion in aged muscle was due, in part, to the collective attenuation of the chronic stimulation-evoked increase in regulatory proteins involved in mediating mitochondrial protein import and biogenesis. Furthermore, adaptations in mitochondrial function were also blunted in old animals. However, chronic contractile activity evoked greater reductions in mitochondrially-mediated proapoptotic signaling in aged muscle. Thus, mitochondrial plasticity is retained in aged animals, however the magnitude of the changes are less compared to young animals due to attenuated molecular processes regulating organelle biogenesis. PMID:20157569

Ljubicic, Vladimir; Joseph, Anna-Maria; Adhihetty, Peter J.; Huang, Julianna H.; Saleem, Ayesha; Uguccioni, Giulia; Hood, David A.

2009-01-01

392

Metformin prevents LYRM1-induced insulin resistance in 3T3-L1 adipocytes via a mitochondrial-dependent mechanism.  

PubMed

We previously proposed that LYR motif containing 1 (LYRM1)-induced mitochondrial reactive oxygen species (ROS) production contributes to obesity-related insulin resistance. Metformin inhibits ROS production and promotes mitochondrial biogenesis in specific tissues. We assessed the effects of metformin on insulin resistance in LYRM1-over-expressing 3T3-L1 adipocytes. Metformin enhanced basal and insulin-stimulated glucose uptake and GLUT4 translocation, reduced IRS-1 and Akt phosphorylation and ROS levels, and affected the expression of regulators of mitochondrial biogenesis in LYRM1-over-expressing adipocytes. Metformin may ameliorate LYRM1-induced insulin resistance and mitochondrial dysfunction in part via a direct antioxidant effect and in part by activating the adenosine monophosphate-activated protein kinase (AMPK)-PGC1/NRFs pathway. PMID:24903160

Qin, Zhen-Ying; Zhang, Min; Dai, Yong-Mei; Wang, Yu-Mei; Zhu, Guan-Zhong; Zhao, Ya-Ping; Ji, Chen-Bo; Qiu, Jie; Cao, Xin-Guo; Guo, Xi-Rong

2014-12-01

393

Both human ferredoxins 1 and 2 and ferredoxin reductase are important for iron-sulfur cluster biogenesis.  

PubMed

Ferredoxins are iron-sulfur proteins that have been studied for decades because of their role in facilitating the monooxygenase reactions catalyzed by p450 enzymes. More recently, studies in bacteria and yeast have demonstrated important roles for ferredoxin and ferredoxin reductase in iron-sulfur cluster assembly. The human genome contains two homologous ferredoxins, ferredoxin 1 (FDX1) and ferredoxin 2 (FDX2--formerly known as ferredoxin 1L). More recently, the roles of these two human ferredoxins in iron-sulfur cluster assembly were assessed, and it was concluded that FDX1 was important solely for its interaction with p450 enzymes to synthesize mitochondrial steroid precursors, whereas FDX2 was used for synthesis of iron-sulfur clusters, but not steroidogenesis. To further assess the role of the FDX-FDXR system in mammalian iron-sulfur cluster biogenesis, we performed siRNA studies on FDX1 and FDX2, on several human cell lines, using oligonucleotides identical to those previously used, along with new oligonucleotides that specifically targeted each gene. We concluded that both FDX1 and FDX2 were important in iron-sulfur cluster biogenesis. Loss of FDX1 activity disrupted activity of iron-sulfur cluster enzymes and cellular iron homeostasis, causing mitochondrial iron overload and cytosolic iron depletion. Moreover, knockdown of the sole human ferredoxin reductase, FDXR, diminished iron-sulfur cluster assembly and caused mitochondrial iron overload in conjunction with cytosolic depletion. Our studies suggest that interference with any of the three related genes, FDX1, FDX2 or FDXR, disrupts iron-sulfur cluster assembly and maintenance of normal cytosolic and mitochondrial iron homeostasis. PMID:22101253

Shi, Yanbo; Ghosh, Manik; Kovtunovych, Gennadiy; Crooks, Daniel R; Rouault, Tracey A

2012-02-01

394

[Mitochondrial myopathies].  

PubMed

The organ most frequently affected in mitochondrial disorders is the skeletal muscle (mitochondrial myopathy). Mitochondrial myopathies may be part of syndromic as well as non-syndromic mitochondrial disorders. Involvement of the skeletal muscle may remain subclinical, may manifest as isolated elevation of the creatine-kinase, or as weakness and wasting of one or several muscle groups. The course of mitochondrial myopathies is usually slowly progressive and only rarely rapidly progressive leading to restriction of mobility and requirement of a wheel chair or even muscular respiratory insufficiency. Frequently reported symptoms of mitochondrial myopathies are permanent tiredness, easy fatigability, muscle aching at rest or already after moderate exercise, muscle cramps, muscle stiffness, fasciculations and muscle weakness. The diagnosis is based on the history, clinical neurologic examination, blood chemical investigations, lactate stress test, electromyography, magnetic resonance imaging, magnetic resonance spectroscopy, muscle biopsy, biochemical investigations of the skeletal muscles, and genetic investigations. Only symptomatic therapy is available and includes physiotherapy and orthopedic supportive devices, diet, symptomatic drug therapy (analgetics, cramp-releasing drugs, antioxidants, lactate-lowering drugs, alternative energy sources, co-factors), avoidance of mitochondrion-toxic drugs, surgery (correction of ptosis or orthopedic problems), and invasive or non-invasive mechanical ventilation. General anesthesia needs to be performed in the same way as in patients with susceptibility for malignant hyperthermia. PMID:19890772

Finsterer, J

2009-11-01

395

Mitochondrial genetics  

PubMed Central

Introduction In the last 10 years the field of mitochondrial genetics has widened, shifting the focus from rare sporadic, metabolic disease to the effects of mitochondrial DNA (mtDNA) variation in a growing spectrum of human disease. The aim of this review is to guide the reader through some key concepts regarding mitochondria before introducing both classic and emerging mitochondrial disorders. Sources of data In this article, a review of the current mitochondrial genetics literature was conducted using PubMed (http://www.ncbi.nlm.nih.gov/pubmed/). In addition, this review makes use of a growing number of publically available databases including MITOMAP, a human mitochondrial genome database (www.mitomap.org), the Human DNA polymerase Gamma Mutation Database (http://tools.niehs.nih.gov/polg/) and PhyloTree.org (www.phylotree.org), a repository of global mtDNA variation. Areas of agreement The disruption in cellular energy, resulting from defects in mtDNA or defects in the nuclear-encoded genes responsible for mitochondrial maintenance, manifests in a growing number of human diseases. Areas of controversy The exact mechanisms which govern the inheritance of mtDNA are hotly debated. Growing points Although still in the early stages, the development of in vitro genetic manipulation could see an end to the inheritance of the most severe mtDNA disease. PMID:23704099

Chinnery, Patrick Francis; Hudson, Gavin

2013-01-01

396

Mitochondrial changes in endometrial carcinoma: Possible role in tumor diagnosis and prognosis (Review).  

PubMed

Endometrial carcinoma (EC) is a solid neoplasia for which a role for mitochondria in cancer progression is currently emerging and yet represents a diagnostic and prognostic challenge. EC is one of the most frequently occurring gynecological malignancies in the Western world whose incidence has increased significantly during the last decades. Here, we review the literature data on mitochondrial changes reported in EC, namely, mitochondrial DNA (mtDNA) mutations, increase in mitochondrial biogenesis and discuss whether they may be used as new cancer biomarkers for early detection and prognosis of this cancer. PMID:25530491

Cormio, Antonella; Cormio, Gennaro; Musicco, Clara; Sardanelli, Anna Maria; Gasparre, Giuseppe; Gadaleta, Maria Nicola

2015-03-01

397

Cytosolic thioredoxin system facilitates the import of mitochondrial small Tim proteins.  

PubMed

Thiol-disulphide redox regulation has a key role during the biogenesis of mitochondrial intermembrane space (IMS) proteins. Only the Cys-reduced form of precursor proteins can be imported into mitochondria, which is followed by disulphide bond formation in the mitochondrial IMS. In contrast to the wealth of knowledge on the oxidation process inside mitochondria, little is known about how precursors are maintained in an import-competent form in the cytosol. Here we provide the first evidence that the cytosolic thioredoxin system is required to maintain the IMS small Tim proteins in reduced forms and facilitate their mitochondrial import during respiratory growth. PMID:22878414

Durigon, Romina; Wang, Qi; Ceh Pavia, Efrain; Grant, Chris M; Lu, Hui

2012-10-01

398

Drp1 is dispensable for mitochondria biogenesis in induction to pluripotency but required for differentiation of embryonic stem cells.  

PubMed

Mature mitochondria with high oxidative phosphorylation undergo fission and fusion and morphogenesis to become immature mitochondria during induced pluripotent stem (iPS) induction from somatic cells. Dynamin-related protein 1 (Drp1) is involved in mitochondria fission and biogenesis in somatic cells. We tested the role of Drp1 in the induction and maintenance of pluripotency. We show that Drp1 band shift occurs in embryonic stem cells (ESCs) and iPS cells (iPSCs) induced from fibroblasts, in association with mitochondrial morphogenesis. However, knockdown of Drp1 by shRNA does not abrogate mitochondria morphogenesis and induction of iPSCs from fibroblasts. Also, knockdown of Drp1 affects neither mitochondria fission and function as shown by normal mitochondrial membrane potential, nor proliferation and pluripotency of ESCs. Nonetheless, Drp1 knockdown negatively influences terminal differentiation of ESCs, particularly in the lineage of neurogenesis in vitro and in vivo, coincident with delayed reduction of Oct4 and Nanog during mid-differentiation. Our data suggest that Drp1 is not critical for mitochondria biogenesis in stem cell proliferation but it is required for neurogenesis likely by downregulation of pluripotency-associated genes Nanog and Oct4. ESC differentiation model could be used to model role of Drp1 in neuron development and diseases. PMID:24937776

Wang, Lei; Ye, Xiaoying; Zhao, Qiang; Zhou, Zhongcheng; Dan, Jiameng; Zhu, Yushan; Chen, Quan; Liu, Lin

2014-10-15

399

Understanding mitochondrial complex I assembly in health and disease.  

PubMed

Complex I (NADH:ubiquinone oxidoreductase) is the largest multimeric enzyme complex of the mitochondrial respiratory chain, which is responsible for electron transport and the generation of a proton gradient across the mitochondrial inner membrane to drive ATP production. Eukaryotic complex I consists of 14 conserved subunits, which are homologous to the bacterial subunits, and more than 26 accessory subunits. In mammals, complex I consists of 45 subunits, which must be assembled correctly to form the properly functioning mature complex. Complex I dysfunction is the most common oxidative phosphorylation (OXPHOS) disorder in humans and defects in the complex I assembly process are often observed. This assembly process has been difficult to characterize because of its large size, the lack of a high resolution structure for complex I, and its dual control by nuclear and mitochondrial DNA. However, in recent years, some of the atomic structure of the complex has been resolved and new insights into complex I assembly have been generated. Furthermore, a number of proteins have been identified as assembly factors for complex I biogenesis and many patients carrying mutations in genes associated with complex I deficiency and mitochondrial diseases have been discovered. Here, we review the current knowledge of the eukaryotic complex I assembly process and new insights from the identification of novel assembly factors. This article is part of a Special Issue entitled: Biogenesis/Assembly of Respiratory Enzyme Complexes. PMID:21924235

Mimaki, Masakazu; Wang, Xiaonan; McKenzie, Matthew; Thorburn, David R; Ryan, Michael T

2012-06-01