title: Elevated mitochondrial oxidative stress impairs metabolic adaptations to exercise in skeletal muscle.
abstract: Mitochondrial oxidative stress is a complex phenomenon that is inherently tied to energy provision and is implicated in many metabolic disorders. Exercise training increases mitochondrial oxidative capacity in skeletal muscle yet it remains unclear if oxidative stress plays a role in regulating these adaptations. We demonstrate that the chronic elevation in mitochondrial oxidative stress present in Sod2 (+/-) mice impairs the functional and biochemical mitochondrial adaptations to exercise. Following exercise training Sod2 (+/-) mice fail to increase maximal work capacity, mitochondrial enzyme activity and mtDNA copy number, despite a normal augmentation of mitochondrial proteins. Additionally, exercised Sod2 (+/-) mice cannot compensate for their higher amount of basal mitochondrial oxidative damage and exhibit poor electron transport chain complex assembly that accounts for their compromised adaptation. Overall, these results demonstrate that chronic skeletal muscle mitochondrial oxidative stress does not impact exercise induced mitochondrial biogenesis, but impairs the resulting mitochondrial protein function and can limit metabolic plasticity.
authors: Department of Kinesiology, McMaster University, Hamilton, Ontario, Canada ; Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada.
authors: Justin D
authors: JD
authors: Crane
authors: Arkan
authors: A
authors: Abadi
authors: Bart P
authors: BP
authors: Hettinga
authors: Daniel I
authors: DI
authors: Ogborn
authors: Lauren G
authors: LG
authors: MacNeil
authors: Gregory R
authors: GR
authors: Steinberg
authors: Mark A
authors: MA
authors: Tarnopolsky
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D004272:DNA, Mitochondrial / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins; D004579:Electron Transport; D006609:High Mobility Group Proteins; D051379:Mice; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000473:pathology* / Q000503:physiopathology*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010805:Physical Conditioning, Animal; D017510:Protein Folding; D013482:Superoxide Dismutase / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D004272:DNA, Mitochondrial; D004268:DNA-Binding Proteins; D006609:High Mobility Group Proteins; D024101:Mitochondrial Proteins; C081930:Tfam protein, mouse; D013482:Superoxide Dismutase