title: The Role of Exercise and TFAM in Preventing Skeletal Muscle Atrophy.
abstract: Skeletal muscle atrophy is the consequence of protein degradation exceeding protein synthesis. This arises for a multitude of reasons including the unloading of muscle during microgravity, post-surgery bedrest, immobilization of a limb after injury, and overall disuse of the musculature. The development of therapies prior to skeletal muscle atrophy settings to diminish protein degradation is scarce. Mitochondrial dysfunction is associated with skeletal muscle atrophy and contributes to the induction of protein degradation and cell apoptosis through increased levels of ROS observed with the loss of organelle function. ROS binds mtDNA, leading to its degradation and decreasing functionality. Mitochondrial transcription factor A (TFAM) will bind and coat mtDNA, protecting it from ROS and degradation while increasing mitochondrial function. Exercise stimulates cell signaling pathways that converge on and increase PGC-1α, a well-known activator of the transcription of TFAM and mitochondrial biogenesis. Therefore, in the present review we are proposing, separately, exercise and TFAM treatments prior to atrophic settings (muscle unloading or disuse) alleviate skeletal muscle atrophy through enhanced mitochondrial adaptations and function. Additionally, we hypothesize the combination of exercise and TFAM leads to a synergistic effect in targeting mitochondrial function to prevent skeletal muscle atrophy. J. Cell. Physiol. 232: 2348-2358, 2017. © 2016 The Authors. Journal of Cellular Physiology Published by © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Physiology, University of Louisville School of Medicine, Louisville, Kentucky.
authors.forename: Nicholas T
authors.identifier: http://orcid.org/0000-0002-9425-1200
authors.initials: NT
authors.lastname: Theilen
authors.affiliation: Department of Physiology, University of Louisville School of Medicine, Louisville, Kentucky.
authors.forename: George H
authors.initials: GH
authors.lastname: Kunkel
authors.affiliation: Department of Physiology, University of Louisville School of Medicine, Louisville, Kentucky.
authors.forename: Suresh C
authors.initials: SC
authors.lastname: Tyagi
mesh_terms: D000818:Animals; D017209:Apoptosis; D004272:DNA, Mitochondrial / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D015444:Exercise; D006801:Humans; D008931:Mitochondria, Muscle / Q000378:metabolism* / Q000473:pathology; D024101:Mitochondrial Proteins / Q000378:metabolism*; D009119:Muscle Contraction; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D009133:Muscular Atrophy / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / Q000378:metabolism; D014176:Protein Biosynthesis; D059748:Proteolysis; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D004272:DNA, Mitochondrial; D004268:DNA-Binding Proteins; D024101:Mitochondrial Proteins; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D017382:Reactive Oxygen Species; C499631:TFAM protein, human; D014157:Transcription Factors