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PubMed1999

Evidence of mitochondrial dysfunction in broilers with pulmonary hypertension syndrome (Ascites): effect of t-butyl hydroperoxide on hepatic mitochondrial function, glutathione, and related thiols.

The purpose of this study was to assess mitochondrial function and glutathione (a mitochondrial antioxidant) in response to oxidative stress in mitochondria in vitro obtained from broilers with and without pulmonary hypertension syndrome (PHS). Liver mitochondria from Control and PHS broilers were incubated with 0, 1, and 5-mM tertiary-butyl hydroperoxide (tBH). Indices of mitochondrial function [the respiratory control ratio (RCR) and the adenosine diphosphate to oxygen ratio (ADP:O)], and levels of mitochondrial and extra-mitochondrial reduced (GSH) and oxidized (GSSG) glutathione, cysteine, cystine, glutamate and cysteinyl-glycine were determined following tBH treatment. Lower RCR and ADP:O values were observed in PHS mitochondria than in controls. Whereas control mitochondria remained coupled (RCR > 2.0), only 3 PHS preparations remained coupled after 60 min of incubation with 5 mM tBH, indicating a greater susceptibility to oxidative stress in PHS mitochondria. The lower RCR in PHS mitochondria was due to increased oxygen consumption during State IV respiration. Oxidative stress following tBH treatment (decreased GSH and increased GSSG) was observed, but there were no differences in GSH or GSSG between control and PHS mitochondria. The PHS mitochondria did exhibit elevated mitochondrial and extramitochondrial cystine than controls, however. The results indicate that PHS mitochondria do not lack antioxidant protection from GSH, but lower RCR and ADP:O ratios in PHS mitochondria indicate a dysfunction that may contribute to the pathophysiology of this metabolic disease in broilers.

Adenosine Diphosphate↗
PubMed1998

The effects of dietary restriction on mitochondrial dysfunction in aging.

Age-associated alterations in the mitochondrial electron transport system (ETS) may lead to free radical generation and contribute to aging. The complexes of the ETS were screened spectrophotometrically in gastrocnemius of young (10 month) as well as older (20 and 26 month) B6C3F1 female mice fed an ad libitum (AL) diet or a restricted (DR) in total calories diet (40% less food than AL mice). The activities of complexes I, III, and IV decreased significantly by 62%, 54%, and 74%, respectively, in old AL mice (AL20) compared to young AL mice (AL10). Complexes I, III, and IV from DR10 mice had activities that were significantly lower than those seen in AL10 mice (suggesting a lower total respiratory rate or improved efficiency). By contrast, complex II activity did not decrease with age (actually increased, but not significantly) in AL20 mice. Complex II was decreased across age in DR mice. K(m) for ubiquinol-2 of complex III was significantly increased in AL10 animals (0.33 mM vs. 0.26 mM in DR10 mice) and was further increased with aging (0.44 mM in AL20 vs. 0.17 mM in DR20 mice). This suggests obstruction of binding, inhibition of electron flow in aging, which could yield premature product release as a free radical. Total complex IV by Vmax was highest in AL10 mice, but the proportion of complex as high-affinity sites was lower (69%) than in either DR10 (80%) or DR20 (80%). The percentage of high-affinity sites decreased to only 45% in AL20 mice, and Vmax was reduced by 75 percent. In AL26 mice high-affinity sites decreased to 33 percent. At physiologic concentration of reduced cytochrome c, significant dysfunction of complex IV in AL20 or AL26 mice would be expected with obstruction of overall electron transport. The age-associated loss of activity and function of complexes I, III, and IV may contribute to increased free radical production. Lack of sufficient DNA repair in mitochondria and juxtaposition to the ETS adds to susceptibility and accumulation of mtDNA and other mitochondrial macromolecular damage. DR seems to retard this deterioration of mitochondrial respiratory function by preserving enzymatic activities and function.

Aging↗
PubMed1993

Iron induced oxidative stress and mitochondrial dysfunction: relevance to Parkinson's disease.

Inactivation of the mitochondrial respiratory chain in response to iron-induced oxidative stress has been studied in cultured cells. Iron loading resulted in malonaldehyde production, decreased levels of glutathione and reduced specific activities of both complexes I and IV of the respiratory chain. These results are discussed with respect to idiopathic Parkinson's disease, which is associated with increased iron levels and a specific decrease in complex I activity in the substantia nigra.

Animals↗
PubMed1991

The effects of fructose on adenosine triphosphate depletion following mitochondrial dysfunction and lethal cell injury in isolated rat hepatocytes.

Mitochondrial injury in aerobic mammalian cells is associated with a rapid depletion of adenosine triphosphate (ATP) which occurs prior to the onset of lethal cell injury. In this report, the relationships between ATP depletion and lethal cell injury were examined in rat hepatocytes using oligomycin as a model mitochondrial toxicant and fructose as an alternative carbohydrate source for glycolysis. Oligomycin was more potent in causing lethal cell injury in hepatocytes isolated from fasted animals than cells from fed animals. The onset of cell injury (leakage of lactate dehydrogenase) in cells from fed animals correlated with the depletion of stored glycogen and ATP. The degree and time course profile of oligomycin-induced ATP depletion could be duplicated with 50 mM fructose alone in hepatocytes from fasted animals; however, fructose did not cause lethal cell injury. Oligomycin caused marked accumulation of adenosine monophosphate (AMP) and inorganic phosphate (Pi) and a conservation of adenine nucleotides. In contrast, fructose (50 mM) caused a decrease in Pi, no persistent change in AMP, and a depletion of the adenine nucleotide pool. Fructose, at concentrations greater than 1.0 mM, protected hepatocytes from oligomycin-induced toxicity. Blockade of mitochondrial ATP synthesis with oligomycin resulted in massive ATP depletion. In the presence of oligomycin, 5.0 mM fructose maintained cellular ATP content similar to that of control cells, whereas 50 mM fructose did not, demonstrating the biphasic effect of increasing fructose concentrations on cellular ATP content. Fructose-induced protection of hepatocytes from oligomycin toxicity was due to glycolytic fructose metabolism as hepatocytes incubated with iodoacetate (30 microM), fructose, and oligomycin had reduced viability and ATP content. In conclusion, interruption of mitochondrial ATP synthesis leads to marked ATP depletion and lethal cell injury. Cell injury is clearly not due to ATP depletion alone since increased glycolytic ATP production from either glycogen or fructose can maintain cell integrity in the absence of mitochondrial ATP synthesis and at low cellular ATP levels.

Adenosine Triphosphate↗
PubMed1981

Increased muscle calcium. A possible cause of mitochondrial dysfunction and cellular necrosis in denervated rat skeletal muscle.

Mitochondrial preparations derived from denervated rat skeletal muscle and paired controls were characterized with respect to their ability to take up externally added Ca2+. The denervated and control muscle homogenates and mitochondrial [Ca2+] were also determined. Our data indicate that the denervated mitochondria are able to take up less Ca2+ than the controls before uncoupling occurs. This defect is associated with elevated [Ca2+] in homogenate and mitochondrial fractions in the denervated state. The causal relationship between Ca2+ overload, mitochondrial functional damage and cell necrosis is discussed.

Animals↗
PubMed2004

Mitochondrial dysfunction as a cause of optic neuropathies.

Mitochondria are increasingly recognized as central players in the life and death of cells and especially of neurons. The energy-dependence of retinal ganglion cells (RGC) and their axons, which form the optic nerve, is singularly skewed. In fact, while mitochondria are very abundant in the initial, unmyelinated part of the axons anterior to the lamina cribrosa, their number suddenly decreases as the myelin sheath begins more posteriorly. The vascular system also presents different blood-brain barrier properties anterior and posterior to the lamina, possibly reflecting the different metabolic needs of the optic nerve head (unmyelinated) and of the retrobulbar optic nerve (myelinated). Mitochondrial biogenesis occurs within the cellular somata of RGC in the retina. It needs the coordinated interaction of nuclear and mitochondrial genomes. Mitochondria are then transported down the axons and distributed where they are needed. These locations are along the unmyelinated portion of the nerve, under the nodes of Ranvier in the retrobulbar nerve, and at the synaptic terminals. Efficient transportation of mitochondria depends on multiple factors, including their own energy production, the integrity of the cytoskeleton and its protein components (tubulin, etc.), and adequate myelination of the axons. Any dysfunction of these systems may be of pathological relevance for optic neuropathies with primary or secondary involvement of mitochondria. Leber's hereditary optic neuropathy (LHON) is the paradigm of mitochondrial optic neuropathies where a primary role for mitochondrial dysfunction is certified by maternal inheritance and association with specific mutations in the mitochondrial DNA (mtDNA). Clinical phenocopies of this pathology are represented by the wide array of optic neuropathies associated with vitamin depletion, toxic exposures, alcohol and tobacco abuse, and use of certain drugs. Moreover, the recent identification of mutations in the nuclear gene OPA1 as the causative factor in dominant optic atrophy (DOA, Kjer's type) brought the unexpected finding that this gene encodes for a mitochondrial protein, suggesting that DOA and LHON may be linked by similar pathogenesis. Polymorphisms in this very same gene may be associated with normal tension glaucoma (NTG), which might be considered a genetically determined optic neuropathy that again shows similarities with both LHON and DOA. Exciting new developments come from first examples of mitochondrial optic neuropathies in animal models that are genetically determined or are the result of ingenious engineering of mitochondrial gene expression, or from biochemical manipulations of the respiratory complexes. Even more exciting is the first successful attempt to correct the LHON-related complex I dysfunction by the allotopic nuclear expression of the recoded mitochondrial gene. There is hope that the genetic complexities, biochemical dysfunctions, and integrated anatomical-physiological cellular relationships will soon be precisely delineated and that promising therapeutic and prophylactic strategies will be proposed.

Animals↗
PubMed2002

Effect of NXY-059 on secondary mitochondrial dysfunction after transient focal ischemia; comparison with cyclosporin A.

The free radical trapping agents NXY-059 and alpha-phenyl-N-tert.-butylnitrone (PBN) markedly reduce infarct volume, even when given 1 or 3 h after the start of recirculation, following 2 h of middle cerebral artery (MCA) occlusion in rats. Their anti-ischemic effects are shared by the two immunosuppressants cyclosporin A (CsA) and FK506. Interestingly, CsA causes an additional reduction in infarct volume when given after only 5 min of recirculation, possibly reflecting blockade of a mitochondrial permeability transition (MPT) pore. PBN, CsA and FK506 are known to ameliorate the secondary dysfunction of mitochondrial function, as assessed in vitro, which occurs during the first 4-6 h of recirculation. The present experiments were undertaken to assess whether NXY-059 reduces tissue damage by acting directly on mitochondrial membranes, and provided that this is the case, if blockade of an MPT is involved. The results were compared to those of CsA, which thus served as a reference compound. NXY-059 was given i.v. after 5 min and 1 h, and CsA after 5 min of recirculation. Both NXY-059 and CsA reduced infarct volumes to about 30% of control, prevented the secondary decline in mitochondrial respiratory function during recirculation, and reduced the mitochondrial release of cytochrome c after 6 and 24 h of recirculation. However, NXY-059 failed to block the effect of Ca(2+) on mitochondrial swelling in vitro, as CsA did. Furthermore, NXY-059, given after 5 min of recirculation, did not reproduce the effects of CsA. The results thus suggest that NXY-059 exerts its effects on mitochondria by indirect mechanisms.

Animals↗
PubMed2004

The role of iNOS in alcohol-dependent hepatotoxicity and mitochondrial dysfunction in mice.

Nitric oxide (NO) is now known to control both mitochondrial respiration and organelle biogenesis. Under conditions of ethanol-dependent hepatic dysfunction, steatosis is increased, and this is associated with increased expression of inducible nitric oxide synthase (iNOS). We have previously shown that after chronic exposure to ethanol, the sensitivity of mitochondrial respiration to inhibition by NO is enhanced, and we have proposed that this contributes to ethanol-dependent hypoxia. This study examines the role of iNOS in controlling the NO-dependent modification of mitochondrial function. Mitochondria were isolated from the livers of both wild-type (WT) and iNOS knockout (iNOS-/-) mice that were fed an isocaloric ethanol-containing diet for a period of 5 weeks. All animals that consumed ethanol showed some evidence of fatty liver; however, this was to a lesser extent in the iNOS-/- mice compared to controls. At this early stage in ethanol-dependent hepatic dysfunction, infiltration of inflammatory cells and the formation of nitrated proteins was also decreased in response to ethanol feeding in the iNOS-/- animals. Mitochondria isolated from wild-type ethanol-fed mice showed a significant decrease in respiratory control ratio and an increased sensitivity to NO-dependent inhibition of respiration relative to their pair-fed controls. In contrast, liver mitochondria isolated from iNOS-/- mice fed ethanol showed no change in the sensitivity to NO-dependent inhibition of respiration. In conclusion, the hepatic response to chronic alcohol-dependent cytotoxicity involves a change in mitochondrial function dependent on the induction of iNOS.

Animals↗
PubMed2005

Increased anxiety-like behaviors and mitochondrial dysfunction in mice with targeted mutation of the Bcl-2 gene: further support for the involvement of mitochondrial function in anxiety disorders.

There is growing evidence that anxiety disorders are associated with impairments of cellular plasticity and resilience. Paralleling these advances in our understanding of the neurobiologic underpinnings of anxiety disorders is the growing appreciation of the diverse functions that mitochondria play in regulating integrated CNS function. The emerging data suggest that mitochondrial Ca2+ sequestration has a key role in modulating the tone of synaptic plasticity in a variety of neuroanatomical regions, including those implicated in the pathophysiology of anxiety disorders. Furthermore, activation of peripheral mitochondrial benzodiazepine receptors resulted in reduced anxiety in rats. One of the major modulators of mitochondrial function is Bcl-2 proteins imbedded in the inner mitochondrial membrane. Bcl-2 overexpression increases mitochondria Ca2+ uptake capacity and resistance to Ca2+-inhibition of respiration and upregulation of Bcl-2 increases maximal uptake capacity of mitochondria. We have, therefore, explored the significance of Bcl-2 in the association between mitochondrial function and affective disorders testing Bcl-2 heterozygote mice in models of affective and anxiety disorders. Mutant mice have reduced mitochondrial Bcl-2 levels, and although they have no gross behavioral abnormalities, they demonstrate a significant increase of anxiety-like behaviors. Bcl-2 heterozygote mice spent less time in the center of an open field, spent less time outside an enclosure in the "emergence test", were less likely to explore the transparent part of a black/white box or the open arms of an elevated plus maze compared with WT controls. Mutant mice did not differ from WT in measures of locomotion or in the forced swim test for depression-like behavior suggesting a specific effect on anxiety-like behaviors. Our study, therefore demonstrates that Bcl-2 may be a key factor in anxiety disorders and that its effects may possibly originate from its role in the mitochondria.

Animals↗
PubMed1993

Age dependence of striatal neuronal death caused by mitochondrial dysfunction.

Several lines of evidence point to a decline in mitochondrial efficiency with age. The relationship between age and sensitivity to Huntington disease-like neuronal death in the striatum induced by the mitochondrial inhibitor 3-nitropropionic acid (3-NP) was examined. 3-NP has been shown to cause degeneration of striatum, hippocampus, and thalamus in rat and of caudate-putamen in humans. We administered single doses of 3-NP intraperitoneally to rats of various ages. Animals older than 4 months exhibited a far greater susceptibility to striatal neurotoxicity and mortality compared with younger animals. These results are discussed in the context of age-dependent metabolic impairment, which may be a key factor in the etiology of neurodegenerative disorders such as Huntington's disease and Alzheimer's disease.

Acetylcholinesterase↗
PubMed2004

A transcriptomic and proteomic characterization of the Arabidopsis mitochondrial protein import apparatus and its response to mitochondrial dysfunction.

Mitochondria import hundreds of cytosolically synthesized proteins via the mitochondrial protein import apparatus. Expression analysis in various organs of 19 components of the Arabidopsis mitochondrial protein import apparatus encoded by 31 genes showed that although many were present in small multigene families, often only one member was prominently expressed. This was supported by comparison of real-time reverse transcriptase-polymerase chain reaction and microarray experimental data with expressed sequence tag numbers and massive parallel signature sequence data. Mass spectrometric analysis of purified mitochondria identified 17 import components, their mitochondrial sub-compartment, and verified the presence of TIM8, TIM13, TIM17, TIM23, TIM44, TIM50, and METAXIN proteins for the first time, to our knowledge. Mass spectrometry-detected isoforms correlated with the most abundant gene transcript measured by expression data. Treatment of Arabidopsis cell culture with mitochondrial electron transport chain inhibitors rotenone and antimycin A resulted in a significant increase in transcript levels of import components, with a greater increase observed for the minor isoforms. The increase was observed 12 h after treatment, indicating that it was likely a secondary response. Microarray analysis of rotenone-treated cells indicated the up-regulation of gene sets involved in mitochondrial chaperone activity, protein degradation, respiratory chain assembly, and division. The rate of protein import into isolated mitochondria from rotenone-treated cells was halved, even though rotenone had no direct effect on protein import when added to mitochondria isolated from untreated cells. These findings suggest that transcription of import component genes is induced when mitochondrial function is limited and that minor gene isoforms display a greater response than the predominant isoforms.

Arabidopsis↗
PubMed1995

Localized mitochondrial dysfunction in canine myocardial ischemia.

Effects of myocardial ischemia on mitochondrial enzymes and mitochondrial DNA (mtDNA) were examined using the model of Ameroid constriction of canine cardiac vessels. Endocardium supplied by constricted coronary arteries was found to have significantly lower citrate synthase and complex IV activities compared to values obtained from either epicardium supplied by constricted vessels or endocardium supplied by unconstricted coronary arteries. Neither significant differences in mtDNA copy number nor changes in respiratory complexes I, III and V were detected. These results suggest that highly localized, specific mitochondrial enzyme changes result from chronic myocardial ischemia.

Animals↗
PubMed2005

Mitochondrial dysfunction in cardiovascular disease.

Whereas the pathogenesis of atherosclerosis has been intensively studied and described, the underlying events that initiate cardiovascular disease are not yet fully understood. A substantial number of studies suggest that altered levels of oxidative and nitrosoxidative stress within the cardiovascular environment are essential in the development of cardiovascular disease; however, the impact of such changes on the subcellular or organellar components and their functions that are relevant to cardiovascular disease inception are less understood. In this regard, studies are beginning to show that mitochondria not only appear susceptible to damage mediated by increased oxidative and nitrosoxidative stress, but also play significant roles in the regulation of cardiovascular cell function. In addition, accumulating evidence suggests that a common theme among cardiovascular disease development and cardiovascular disease risk factors is increased mitochondrial damage and dysfunction. This review discusses aspects relating mitochondrial damage and function to cardiovascular disease risk factors and disease development.

Animals↗
PubMed2026

Differential contributions of mt-Tr and Cs variants to developmental cochlear defects and mitochondrial dysfunction in A/J mice.

A/J mice exhibit early-onset hearing loss linked to Cdh23, mitochondrial tRNA-Arg (mt-Tr), and citrate synthase (Cs) variants. Although developmental cochlear defects have been identified in juvenile A/J mice, the hierarchical contributions of mt-Tr versus Cs remain unclear. Using reciprocal intercross-derived strains to decouple mitochondrial haplotypes from nuclear factors, we demonstrate that the mitochondrial background is the primary determinant of auditory dysfunction. Mice with A/J mtDNA (AXB strains) displayed significantly higher ABR thresholds, accelerated hair cell attrition, and severe stereocilia dysmorphology compared to those with B6 mtDNA (BXA strains), occurring largely independently of the Cs genotype. While the Cs mutation exacerbated hearing loss, its impact was secondary to that of the dominant mitochondrial background. Systemic behavioral assessments and mitochondrial assays confirmed that A/J mitochondria exert a more profound metabolic impact than the Cs mutation. Our findings establish that the mitochondrial genomic background, with the mt-Tr locus as a prominent candidate variant, serves as the principal driver of developmental cochlear defects and early-onset hearing loss in A/J mice, while the nuclear Cs mutation acts as a synergistic modifier. This study underscores the critical role of mitonuclear crosstalk in inner ear maturation and provides new insights into the etiology of hereditary hearing loss.

Animals↗
PubMed2000

Nitric oxide production and mitochondrial dysfunction during rat thymocyte apoptosis.

Production of nitric oxide (NO) by mitochondrial membranes as methemoglobin formation sensitive to N(G)-methyl-l-arginine inhibition and mitochondrial O(2) consumption in metabolic states 3 and 4 and the respiratory control (state 3/state 4) were measured at early stages of rat thymocyte apoptosis. Programmed cell death was induced by addition of methylprednisolone and etoposide to thymocyte suspensions. Increased NO production by mitochondrial membranes was observed after 30 min of methylprednisolone and etoposide addition and was accompanied by mitochondrial respiratory impairment as an early phenomenon in apoptotic thymocytes. The respiratory control in isolated mitochondria from untreated thymocytes was 4.2 +/- 0.2 and decreased to 3.1 +/- 0.2 and 1.9 +/- 0.3 after 1 h of methylprednisolone and etoposide treatment, respectively. The low mitochondrial respiratory control was accompanied by a marked decrease in GSH and cytochrome c content. Moreover, an inhibitory effect in the amount of apoptosis due to thymocyte pretreatment with N(G)-methyl-l-arginine and N(omega)-nitro-(l)-arginine (l-NNA), indicate that nitric oxide production is closely involved in the signaling of rat thymocyte apoptosis.

Animals↗
PubMed1998

Cardiac reperfusion injury: aging, lipid peroxidation, and mitochondrial dysfunction.

Cardiac reperfusion and aging are associated with increased rates of mitochondrial free radical production. Mitochondria are therefore a likely site of reperfusion-induced oxidative damage, the severity of which may increase with age. 4-Hydroxy-2-nonenal (HNE), a major product of lipid peroxidation, increases in concentration upon reperfusion of ischemic cardiac tissue, can react with and inactivate enzymes, and inhibits mitochondrial respiration in vitro. HNE modification of mitochondrial protein(s) might, therefore, be expected to occur during reperfusion and result in loss in mitochondrial function. In addition, this process may be more prevalent in aged animals. To begin to test this hypothesis, hearts from 8- and 24-month-old rats were perfused in Langendorff fashion and subjected to periods of ischemia and/or reperfusion. The rate of state 3 respiration of mitochondria isolated from hearts exposed to ischemia (25 min) was approximately 25% less than that of controls, independent of age. Reperfusion (40 min) caused a further decline in the rate of state 3 respiration in hearts isolated from 24- but not 8-month-old rats. Furthermore, HNE modification of mitochondrial protein (approximately 30 and 44 kDa) occurred only during reperfusion of hearts from 24-month-old rats. Thus, HNE-modified protein was present in only those mitochondria exhibiting reperfusion-induced declines in function. These studies therefore identify mitochondria as a subcellular target of reperfusion damage and a site of age-related increases in susceptibility to injury.

Aging↗
PubMed2000

[Roles of mitochondrial dysfunctions in Alzheimer's disease--contribution of deficiency of ALDH 2].

Mitochondrial aldehyde dehydrogenase 2 (ALDH 2) deficiency is caused by a mutant allele in the Mongoloids. To examine whether genetic constitutions affecting aldehyde metabolism influence the risk for late-onset Alzheimer's disease (LOAD), we performed a case-control study in the Japanese population on the deficiency in ALDH 2 caused by the dominant-negative mutant allele of the ALDH 2 gene (ALDH 2 * 2). In a comparison of 447 patients with sex, age and region matched non-demented controls, the genotype frequency carrying the ALDH 2 * 2 allele was significantly higher in the patients than in the controls (p = 0.001, Odds ratio 1.6). Logistic regression analysis indicates that carriage of the ALDH 2 * 2 allele is an independent risk for LOAD of the epsilon 4 allele of the apolipoprotein E gene (APOE-epsilon 4) (p = 0.002). Moreover, the odds ratio for LOAD in carriers of the ALDH 2 * 2 allele was almost twice that in non-carriers irrespective of status with regard to the APOE-epsilon 4 allele. Among patients homozygous for the APOE-epsilon 4 allele, age at onset of LOAD was significantly lower in those with than without the ALDH 2 * 2 allele. In addition, dosage of the ALDH 2 * 2 allele significantly affected age at onset of patients homozygous for the APOE-epsilon 4 allele. These results indicate that the ALDH 2 deficiency is a risk for LOAD, synergistically acting with the APOE-epsilon 4 allele.

Age of Onset↗
PubMed2004

Structural manifestations of mitochondrial dysfunction in skeletal muscles of early aging OXYS rats.

Changes in the mitochondrial compartment are the central element in the morphogenesis of musculoskeletal abnormalities in early aging OXYS rats. Compensatory hyperplasia and hypertrophy with enlargement of the working surface area are seen in these organelles at the age of 2 months. The mitochondria are characterized by polymorphism, compact packing of cristae. By the age of 9 months destructive changes and sharp reduction of the mitochondrial compartment are observed is many myocytes. Disorders in the mitochondrial structure and function and oxidative stress can be among the causes of degenerative changes in the myofibrillar system and other structures of muscle fibers, including those resultant from activation of apoptosis.

Aging↗