title: Endurance exercise is protective for mice with mitochondrial myopathy.
abstract: Defects in the mitochondrial ATP-generating system are one of the most commonly inherited neurological disorders, but they remain without treatment. We have recently shown that modulation of the peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha) level in skeletal muscle of a mitochondrial myopathy mouse model offers a therapeutic approach. Here we analyzed if endurance exercise, which is known to be associated with an increased PGC-1alpha level in muscle, offers the same beneficial effect. We subjected male and female mice that develop a severe mitochondrial myopathy due to a cytochrome-c oxidase deficiency at 3 mo of age to endurance exercise training and monitored phenotypical and metabolic changes. Sedentary myopathy and wild-type mice were used as controls. Exercise increased PGC-1alpha in muscle, resulting in increased mitochondrial biogenesis, and successfully stimulated residual respiratory capacity in muscle tissue. As a consequence, ATP levels were increased in exercised mice compared with sedentary myopathy animals, which resulted in a delayed onset of the myopathy and a prolonged lifespan of the exercised mice. As an added benefit, endurance exercise induced antioxidant enzymes. The overall protective effect of endurance exercise delayed the onset of the mitochondrial myopathy and increased life expectancy in the mouse model. Thus stimulating residual oxidative phosphorylation function in the affected muscle by inducing mitochondrial biogenesis through endurance exercise might offer a valuable therapeutic intervention for mitochondrial myopathy patients.
authors.affiliation: Dept. of Neurology, Miller School of Medicine, Univ. of Miami, 1095 NW 14th Terrace, Miami, FL 33136, USA.
authors.forename: Tina
authors.initials: T
authors.lastname: Wenz
authors.forename: Francisca
authors.initials: F
authors.lastname: Diaz
authors.forename: Dayami
authors.initials: D
authors.lastname: Hernandez
authors.forename: Carlos T
authors.initials: CT
authors.lastname: Moraes
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D019883:Alkyl and Aryl Transferases / Q000172:deficiency / Q000235:genetics; D000818:Animals; D030401:Cytochrome-c Oxidase Deficiency / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D008136:Longevity; D008297:Male; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008931:Mitochondria, Muscle / Q000502:physiology*; D017240:Mitochondrial Myopathies / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D010088:Oxidoreductases / Q000096:biosynthesis; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010805:Physical Conditioning, Animal / Q000502:physiology*; D012146:Rest / Q000502:physiology; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors
chemical_list: D008565:Membrane Proteins; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; D000255:Adenosine Triphosphate; D010088:Oxidoreductases; D019883:Alkyl and Aryl Transferases; C512252:COX10 protein, mouse