Abstract Significance: Parkinson's disease (PD) is a prevalent neurodegenerative disease affecting millions of individuals worldwide. Despite intensive efforts devoted to drug discovery, the disease remains incurable. To provide more effective medical therapy for PD, better understanding of the underlying causes of the disease is clearly necessary. Recent Advances: A broad range of studies ...

Lysosomal storage diseases (LSDs) are a class of genetic disorders in which proteins responsible for digestion or absorption of endocytosed material do not function or do not localize properly. The resulting cellular "indigestion" causes buildup of intracellular storage inclusions that contain unprocessed lipids and proteins that form macromolecular complexes. The buildup of storage material is ...

While the etiology of Parkinson's disease remains largely elusive, there is accumulating evidence suggesting that mitochondrial dysfunction occurs prior to the onset of symptoms in Parkinson's disease. Mitochondria are remarkably primed to play a vital role in neuronal cell survival since they are key regulators of energy metabolism (as ATP producers), of intracellular calcium ...

Mutations in superoxide dismutase (SOD1) are causative for inherited amyotrophic lateral sclerosis. A proportion of SOD1 mutant protein is misfolded onto the cytoplasmic face of mitochondria in one or more spinal cord cell types. By construction of mice in which mitochondrially targeted enhanced green fluorescent protein is selectively expressed in motor neurons, we ...

Mutations in superoxide dismutase (SOD1) are causative for inherited amyotrophic lateral sclerosis. A proportion of SOD1 mutant protein is misfolded onto the cytoplasmic face of mitochondria in one or more spinal cord cell types. By construction of mice in which mitochondrially targeted enhanced green fluorescent protein is selectively expressed in motor neurons, we ...

... The loss of TACI expression in prostate cells therefore conceivably results in an imbalance in homeostasis resulting in the aberrant accumulation of ...

... The loss of TACI expression in prostate cells therefore conceivably results in an imbalance in homeostasis resulting in the aberrant accumulation of ...

The complex cytopathology of mitochondrial diseases is usually attributed to insufficient ATP. AMP-activated protein kinase (AMPK) is a highly sensitive cellular energy sensor that is stimulated by ATP-depleting stresses. By antisense-inhibiting chaperonin 60 expression, we produced mitochondrially diseased strains with gene dose-dependent defects in ...

Carnitines are involved in mitochondrial transport of fatty acids and are of critical importance for maintaining normal mitochondrial function. This review summarizes recent experimental and clinical studies showing that mitochondrial dysfunction secondary to a disruption of carnitine homeostasis may play a role in ...

The role of mitochondria as a nexus of developmental regulation in mammalian oogenesis and early embryogenesis is emerging from basic research in model species and from clinical studies in infertility treatments that require in vitro fertilization and embryo culture. Here, mitochondrial bioenergetic activities and roles in calcium homeostasis, regulation ...

... Abstract : The stress of large thermal injuries initiates alterations of body homeostasis which are primarily catabolic in nature and which manifest as ...

... energy production and electrolyte homeostasis, impairment of mitochondrial function by nanoparticles may have drastic ...

Adenosine monophosphate-activated protein kinase (AMPK) is a conserved sensor of intracellular energy activated in response to low nutrient availability and environmental stress. In a screen for conserved substrates of AMPK, we identified ULK1 and ULK2, mammalian orthologs of the yeast protein kinase Atg1, which is required for autophagy. Genetic analysis of AMPK or ULK1 in mammalian liver and C. ...

The role of mitochondrial dysfunction and oxidative stress has been extensively characterized in the aetiology of sarcopenia (aging-associated loss of muscle mass) and muscle wasting as a result of muscle disuse. What remains less clear is whether the decline in skeletal muscle mitochondrial oxidative capacity is purely a function of the aging process or ...

The role of mitochondrial dysfunction and oxidative stress has been extensively characterized in the aetiology of sarcopenia (aging-associated loss of muscle mass) and muscle wasting as a result of muscle disuse. What remains less clear is whether the decline in skeletal muscle mitochondrial oxidative capacity is purely a function of the aging process or ...

Neuronal cell death in a number of neurological disorders is associated with aberrant mitochondrial dynamics and mitochondrial degeneration. However, the triggers for this mitochondrial dysregulation are not known. Here we show excessive mitochondrial fission and ...

Brain aging is associated with a progressive imbalance between antioxidant defenses and intracellular concentrations of reactive oxygen species (ROS) as exemplified by increases in products of lipid peroxidation, protein oxidation, and DNA oxidation. Oxidative conditions cause not only structural damage but also changes in the set points of redox-sensitive signaling processes including the insulin ...

... We believe this is an example of tissue homeostasis, in which the normal mammary epithelial cells regulate the growth of aberrant epithelial cells. ...

Tickled PINK1: Mitochondrial homeostasis and autophagy in recessive Parkinsonism Charleen T. Chu-fusion machinery, but also by regulation of biogenesis, axonal/dendritic transport and autophagy. A working model/respiratory dysfunction and destabilization of calcium homeostasis, which trigger compensatory fission, autophagy

The stress of large thermal injuries initiates alterations of body homeostasis which are primarily catabolic in nature and which manifest as increased metabolic rate, erosion, of body mass, loss of nitrogen in the urine, and abnormalities of carbohydrate ...

... when investigating cell viability, mitochondrial function, calcium homeostasis, apoptosis, cytoskeleton, reactive oxygen species, glutathione levels, bile acid ...

Mutations of thymidine kinase 2 (TK2), an essential component of the mitochondrial nucleotide salvage pathway, can give rise to mitochondrial DNA (mtDNA) depletion syndromes (MDS). These clinically heterogeneous disorders are characterized by severe reduction in mtDNA copy number in affected tissues and are associated with progressive myopathy, hepatopathy ...

Mitochondria are crucial in different intracellular pathways of signal transduction. Mitochondria are capable of decoding a variety of extracellular stimuli into markedly different intracellular actions, ranging from energy production to cell death. The fine modulation of mitochondrial calcium (Ca(2+)) homeostasis plays a fundamental role in many of the ...

Cellular homeostasis is linked tightly to mitochondrial functions. Some damage to mitochondrial proteins and nucleic acids can lead to the depolarization of the inner mitochondrial membrane, thereby sensitizing impaired mitochondria for selective elimination by autophagy. Mitochondrial ...

Several enzymes of the metabolic pathways responsible for metabolism of cytosolic ribonucleotides and deoxyribonucleotides are located in mitochondria. Studies described in this paper suggest dysfunction of the mitochondria to affect these metabolic pathways and limit the available levels of cytosolic ribonucleotides and deoxyribonucleotides, which in turn can result in ...

Adenosine monophosphate-activated protein kinase (AMPK) is a conserved sensor of intracellular energy activated in response to low nutrient availability and environmental stress. In a screen for conserved substrates of AMPK, we identified ULK1 and ULK2, mammalian orthologs of the yeast protein kinase Atg1, which is required for autophagy. Genetic analysis of AMPK or ULK1 in mammalian liver and ...

The central nervous system is notable for its level of oxygen utilization and ATP synthesis, resulting in a distinct susceptibility to oxidative stress. Generation of reactive oxygen species (ROS) can occur with mitochondrial respiration as well as during other aspects of cellular homeostasis maintained through a balance between biosynthesis and ...

Skeletal muscle plays an important role in the regulation of energy homeostasis; therefore, the ability of skeletal muscle to adapt and alter metabolic gene expression in response to changes in physiological demands is critical for energy balance. Individuals with cervical spinal cord lesions are characterized by tetraplegia, impaired thermoregulation, and altered skeletal ...

SUMMARYAge-related neurodegenerative diseases are associated with mild impairment of oxidative metabolism and accumulation of abnormal proteins. Within the cell, the mitochondria appears to be a dominant site for initiation and propagation of disease processes. Shifts in metabolism in response to mild metabolic perturbations may decrease the threshold for irreversible injury in response to ...

The pathogenesis of nonalcoholic steatohepatitis (NASH) is poorly understood and the mechanisms are still being elucidated. Mitochondrial dysfunction participates at different levels in NASH pathogenesis since it impairs fatty liver homeostasis and induces overproduction of free radicals that in turn trigger lipid peroxidation and cell death. In this ...

Apoptosis (programmed cell death) is a fundamental process involved in homeostasis and the biological response to anti-tumor therapy. Aberrant expression of apoptotic regulators, such as Bax-a, Bcl-2 and p53 has been associated with breast cancer carcinog...

The gastrointestinal immune system is a major component of the mucosal barrier, which maintains an immunologic homeostasis between the host and the harsh environment of the gut. This homeostasis is achieved by immunologic quiescence, and its dysregulation is thought to result from the development of immune diseases such as food allergies. Recent findings ...

Mechanisms underlying the mitochondrial protection of Limonium sinense extracts (LSE) was studied in lipopolysaccharide and D-galactosamine (LPS/D-GalN) intoxicated mice. It was found that increased activities of serum aspartate aminotransferase and alanine aminotransferase induced by LPS/D-GalN were significantly inhibited by pretreatment with LSE. The obvious disruption of ...

Nitric oxide (NO) and other reactive nitrogen species target multiple sites in the mitochondria to influence cellular bioenergetics and survival. Kinetic imaging studies revealed that NO from either activated macrophages or donor compounds rapidly diffuses to the mitochondria, causing a dose-dependent progressive increase in NO-dependent DAF fluorescence, which corresponded to ...

Nitric oxide and other reactive nitrogen species target multiple sites in the mitochondria to impact cellular bioenergetics and survival. Kinetic imaging studies revealed that NO from either activated macrophages or donor compounds rapidly diffuses to the mitochondria, causing a dose dependent progressive increase in NO-dependent DAF fluorescence that corresponded to ...

Alterations in mitochondrial homeostasis have been implicated in the etiology of Parkinson disease (PD) as demonstrated by human tissue studies, cell culture and in vivo genetic and toxin models. Mutations in the genes encoding PTEN-induced kinase 1 (PINK1), Omi/HtrA2 and parkin contribute to rare forms of parkinsonian neurodegeneration. Recently, each of ...

Mitochondrial membrane hyperpolarization and morphological changes are important in inflammatory cell activation. Despite the pathophysiological relevance, no valid and reproducible method for measuring mitochondrial homeostasis in human inflammatory cells is currently available. This study's purpose was to define and validate ...

Abnormal neuronal calcium (Ca²⁺) homeostasis has been implicated in numerous diseases of the nervous system. The pathogenesis of two increasingly common disorders of the peripheral nervous system, namely neuropathic pain and diabetic polyneuropathy, has been associated with aberrant Ca²⁺ channel expression and ...

By producing ATP and regulating intracellular calcium levels, mitochondria are vital for the function and survival of neurons. Oxidative stress and damage to mitochondrial DNA during the aging process can impair mitochondrial energy metabolism and ion homeostasis in neurons, thereby rendering them vulnerable to degeneration. ...

Maintenance of protein quality control and turnover is essential for cellular homeostasis. In plant organelles this biological process is predominantly performed by ATP-dependent proteases. Here, a genetic screen was performed that led to the identification of Arabidopsis thaliana Lon1 protease mutants that exhibit a post-embryonic growth retardation phenotype. Translational ...

SummaryMitochondrial homeostasis reflects a dynamic balance between membrane fission and fusion events thought essential for mitochondrial function. We report here that altered expression of the C. elegans BCL2 homolog CED-9 affects both mitochondrial fission and fusion. Although striated muscle cells lacking CED-9 ...

BackgroundBipolar disorder (BPD) is characterized by altered intracellular calcium (Ca²⁺) homeostasis. Underlying mechanisms involve dysfunctions in endoplasmic reticulum (ER) and mitochondrial Ca²⁺ handling, potentially mediated by B-cell lymphoma 2 (Bcl-2), a key protein that regulates ...

Under pathophysiological conditions such as obesity, excessive oxidation of nutrients may induce mitochondrial stress, leading to mitochondrial unfolded protein response (UPR(mt)) and initiation of a retrograde stress signaling pathway. Defects in the UPR(mt) and the retrograde signaling pathways may disrupt the integrity and ...

A controlled regulation of mitochondrial mass through either the production (biogenesis) or the degradation (mitochondrial quality control) of the organelle represents a crucial step for proper mitochondrial and cell function. Key steps of mitochondrial biogenesis and quality control are overviewed, with an ...

microscopy rendering of polyketal particles (yellow) retained in the myocardium several days following, "Autophagy in Cancer Cell Survival and Mitochondrial Homeostasis." 11:00-12:00 PM, Cherry Emerson Room 320

... et al 1999). Gaining new roles in neoplasia Apoptosis or programmed cell death is a central regulator of tissue homeostasis. Genetic ... linked to tumor development and progression. Resistance to apopto...

In addition to their well-established role in providing the cell with ATP, mitochondria are the source of iron-sulfur clusters (ISCs) and heme � prosthetic groups that are utilized by proteins throughout the cell in various critical processes. The post-transcriptional system that mammalian cells use to regulate intracellular iron homeostasis depends, in part, upon the ...

Mitochondrial signaling is an information channel between the mitochondrial respiratory chain and the nucleus for the transduction signals regarding the functional state of the mitochondria. The present review examines the question whether radiation of visible and near-IR (IR-A) radiation can activate this retrograde-type cellular signaling pathway. ...

Mitochondria fulfill a number of essential cellular functions, being recognized that the strict regulation of the structure, function and turnover of these organelles is an immutable control node for the maintenance of neuronal integrity and homeostasis. Many lines of evidence posit that mitochondria constitute a convergence point of preconditioning - a paradigm that affords ...

Transition metal deficiency has a strong impact on the growth and survival of an organism. Indeed, transition metals, such as iron, copper, manganese and zinc, constitute essential cofactors for many key cellular functions. Both photosynthesis and respiration rely on metal cofactor-mediated electron transport chains. Chloroplasts and mitochondria are, therefore, organelles with high metal ion ...

In this study, we have identified a novel mitochondrial ubiquitin ligase, designated MITOL, which is localized in the mitochondrial outer membrane. MITOL possesses a Plant Homeo-Domain (PHD) motif responsible for E3 ubiquitin ligase activity and predicted four-transmembrane domains. MITOL displayed a rapid degradation by autoubiquitination activity in a ...

For >20 years, the enigmatic behavior of plant mitochondrial genomes has been well described but not well understood. Chimeric genes appear, and occasionally are differentially replicated or expressed, with significant effects on plant phenotype, most notably on male fertility, yet the mechanisms of DNA replication, chimera formation, and recombination have remained ...

Aplastic anaemia (AA) is a disease characterised by bone marrow hypocellularity and peripheral blood pancytopenia. AA is also associated with mitochondrial aberrations. The present study was undertaken primarily to test the hypothesis that a nutrient mixture could affect the nutritional rehabilitation of mitochondrial ...

chaperones work to- gether, along with other proteins, in the processes of iron- sulfur center biogenesis and mitochondrial iron homeostasis (1, 2). These chaperones, the Hsp70 Ssq1, and the J-protein Jac1 are localized are two chaperones, Hsc66, an Hsp70 and Hsc20, a J-type protein (10, 11), along with IscU, the protein

Sirtuins have emerged in recent years as critical regulators of metabolism, influencing numerous facets of energy and nutrient homeostasis. Here, we review recent advances on the role of this fascinating family of mammalian proteins and their well-orchestrated function in modulating mitochondrial activity. PMID:21641544

Ischemia (I) and reperfusion (R) trigger a series of events, which culminate in severe injury to the transplanted organ. Cell death resulting from the formation of mitochondrial reactive oxygen species (ROS) coupled with the perturbation of mitochondrial Ca2+ homeostasis is central to the development of IR-associated tissue damage. We ...

The objective of the present study was to delineate the molecular mechanisms for mitochondrial contribution to oxidative stress induced by hypoxia and reoxygenation in the heart. The present study introduces a novel model allowing real-time studying mitochondria under hypoxia and reoxygenation, and describes the significance of intramitochondrial calcium ...

Mitochondrial creatine kinase (mtCK) binding to the mitochondrial inner membrane largely determines its biological functions in cellular energy homeostasis, mitochondrial physiology, and dynamics. The membrane binding mechanism is, however, not completely understood. Recent data suggest that a hydrophobic component ...

Mitochondrial dysfunction and endoplasmic reticulum (ER) stress are closely associated with ?-cell dysfunction and peripheral insulin resistance. Thus, each of these factors contributes to the development of type 2 diabetes mellitus (DM). The accumulated evidence reveals structural and functional communications between mitochondria and the ER. It is now well established that ...

Mitochondrial dysfunction and endoplasmic reticulum (ER) stress are closely associated with ?-cell dysfunction and peripheral insulin resistance. Thus, each of these factors contributes to the development of type 2 diabetes mellitus (DM). The accumulated evidence reveals structural and functional communications between mitochondria and the ER. It is now well established that ...

Friedreich's ataxia (FA) is an autosomal recessive disease caused by decreased expression of the mitochondrial protein frataxin. The biological function of frataxin is unclear. The homologue of frataxin in yeast, YFH1, is required for cellular respiration and was suggested to regulate mitochondrial iron homeostasis. Patients ...

The alterations of mitochondrial membrane potential during the development of irreversible cell damage were investigated by measuring rhodamine-123 uptake and distribution in primary cultures as well as in suspensions of rat hepatocytes exposed to different toxic agents. Direct and indirect mechanisms of mitochondrial damage have been identified and a role ...

Mitochondria are important organelles that supply energy to the cell. However, these organelles are also the major source of cellular reactive oxygen species (ROS). Thus, the elimination of damaged or excess mitochondria is essential for maintaining cellular homeostasis. Selective autophagy of mitochondria (mitophagy) plays an important role in the quality control of ...

In order to satisfy the metabolic and ion homeostasis demands of neurons, mitochondria must be transported to appropriate locations within cells. Although it is well established that much of this trafficking occurs on microtubules and, to a lesser extent, actin, the mechanisms by which the trafficking of mitochondria is controlled are poorly understood. A recent study by Chada ...

Mitochondrial function is integral to maintaining cellular homeostasis through the production of ATP, the generation of reactive oxygen species (ROS) for signaling, and the regulation of the apoptotic cascade. A number of small molecules, including nitric oxide (NO), are well characterized regulators of mitochondrial function. Nitrite, ...

Protein homeostasis refers to the ability of cells to generate and regulate the levels of their constituent proteins in terms of conformations, interactions, concentrations and cellular localisation. We discuss here an approach in which physico-chemical properties of proteins and their environments are used to understand the underlying principles governing this process, which ...

Recent findings link metabolic transformation of cancer cells to aberrant functions of mitochondrial uncoupling proteins (UCPs). By inducing proton leak, UCPs interfere with mitochondrial synthesis of adenosine 5'-triphosphate, which is also a key determinant of glycolytic pathways. In addition, UCP suppress the generation of ...

In Down's syndrome there is evidence that increased gene expression coding for specific cystathionine beta-synthase translates directly into biochemical aberrations, which result in a biochemical and metabolic imbalance of the methyl status. This event is destined to impact mitochondrial function since methylation is a necessary event in mitochondria and ...

Diverse age-associated neurodegenerative disorders are featured at a molecular level by depositions of self-aggregating molecules, as represented by amyloid beta peptides (Abeta) and tau proteins in Alzheimer's disease, and cascade-type chain reactions are supposedly commenced with biochemical aberrancies of these amyloidogenic components. Mutagenesis and multiplication of the ...

Axonal degeneration is a prominent pathological feature in multiple sclerosis observed over a century ago. The gradual loss of axons is thought to underlie irreversible clinical deficits in this disease. The precise mechanisms of axonopathy are poorly understood, but likely involve excess accumulation of Ca ions. In healthy fibers, ATP-dependent pumps support homeostasis of ...

In this mini-review/opinion article we describe evidence that multiple cellular and molecular alterations in Alzheimer's disease (AD) pathogenesis involve perturbed cellular calcium regulation, and that alterations in synaptic calcium handling may be early and pivotal events in the disease process. With advancing age neurons encounter increased oxidative stress and impaired energy metabolism, ...

Integration of cell adhesive, survival, and proliferative processes is essential for capillary morphogenesis of endothelial cells (EC) in vitro and vascular development and function in vivo. Unfortunately, the molecular and cellular mechanisms that impact these processes are poorly defined. Here we examined how lack of bim and/or bcl-2 expression impact lung EC function. The absence of bcl-2 or ...

Long Term Potentiation (LTP) is a leading candidate mechanism for learning and memory and is also thought to play a role in the progression of seizures to intractable epilepsy. Maintenance of LTP requires RNA transcription, protein translation and signaling through the mammalian Target of Rapamycin (mTOR) pathway. In peripheral tissue, the energy sensor AMP-activated Protein Kinase (AMPK) ...

The ligand-dependent competing actions of nuclear receptor (NR)-associated transcriptional corepressor and coactivator complexes allow for the precise regulation of NR-dependent gene expression in response to both temporal and environmental cues. Here we report the mouse model termed silencing mediator of retinoid and thyroid hormone receptors (SMRT)(mRID1) in which targeted disruption of the ...

The ligand-dependent competing actions of nuclear receptor (NR)-associated transcriptional corepressor and coactivator complexes allow for the precise regulation of NR-dependent gene expression in response to both temporal and environmental cues. Here we report the mouse model termed silencing mediator of retinoid and thyroid hormone receptors (SMRT)^mRID1 in which targeted ...

Sequestration of calcium by mitochondria is an important mechanism to maintain normal intracellular calcium homeostasis. Anoxic or toxic damage to these organelles has been postulated to disrupt intracellular calcium compartmentalization, leading to cell death. The authors examined the potential relationship between mitochondrial dysfunction, altered ...

SummaryMutations in PINK1 cause autosomal recessive Parkinson's disease. PINK1 is a mitochondrial kinase of unknown function. We investigated calcium homeostasis and mitochondrial function in PINK1-deficient mammalian neurons. We demonstrate physiologically that PINK1 regulates calcium efflux from the mitochondria via the ...

Coupled cellular respiration requires that ATP and ADP be efficiently exchanged between the cytosol and the mitochondrial matrix. When growth factors are withdrawn from dependent cells, metabolism is disrupted by a defect in ATP/ADP exchange across the mitochondrial membranes. Unexpectedly, we find that this defect results from loss of outer ...

Mitofusin-2 (Mfn-2) is a dynamin-like protein that is involved in the rearrangement of the outer mitochondrial membrane. Research using various experimental systems has shown that Mfn-2 is a mediator of mitochondrial fusion, an evolutionarily conserved process responsible for the surveillance of mitochondrial ...

BackgroundMice, whose ribosomal protein S6 cannot be phosphorylated due to replacement of all five phosphorylatable serine residues by alanines (rpS6^P?/?), are viable and fertile. However, phenotypic characterization of these mice and embryo fibroblasts derived from them, has established the role of these modifications in the regulation of the size of several cell types, as ...

The mitochondrial contribution to the maintenance of human embryonic stem cell (hESC) pluripotency and culture homeostasis remains poorly understood. Here, we sought to determine whether hESC adaptation to different feeder-free culture conditions is linked to a mitochondrial adaptation. The expression of ESC pluripotency factors and ...

An analysis was performed of cytogenetic homeostasis in liquidators of the Chernobyl accident after-effects, which led to the belief that if the above contingent of subjects continue living in large industrial regions characterized by high levels of environmental contamination with industrial waste, such as that formed in the chemical, by-product coke, and metallurgical ...

Mitochondria are essential organelles for neuronal survival and play important roles in ATP generation, calcium buffering, and apoptotic signaling. Due to their extreme polarity, neurons utilize specialized mechanisms to regulate mitochondrial transport and retention along axons and near synaptic terminals where energy supply and calcium homeostasis are in ...

In this study, we investigated the effects of biapigenin, a biflavone present in the extracts of Hypericum perforatum, in rat brain mitochondrial bioenergetics and calcium homeostasis. We found that biapigenin significantly decreased adenosine diphosphate (ADP)-induced membrane depolarization and increased repolarization (by 68 and 37%, respectively). ...

BackgroundPTEN-induced kinase 1 (PINK1) is linked to recessive Parkinsonism (EOPD). Pink1 deletion results in impaired dopamine (DA) release and decreased mitochondrial respiration in the striatum of mice. To reveal additional mechanisms of Pink1-related dopaminergic dysfunction, we studied Ca²⁺ vulnerability of purified brain mitochondria, DA levels and ...

Loss-of-function mutations in the gene encoding the mitochondrial PTEN-induced putative kinase 1 (PINK1) are a major cause of early-onset familial Parkinson's disease (PD). Recent studies have highlighted an important function for PINK1 in clearing depolarized mitochondria by mitophagy. However, the role of PINK1 in mitochondrial and cellular functioning ...