title: Unravelling the mechanisms regulating muscle mitochondrial biogenesis.
abstract: Skeletal muscle is a tissue with a low mitochondrial content under basal conditions, but it is responsive to acute increases in contractile activity patterns (i.e. exercise) which initiate the signalling of a compensatory response, leading to the biogenesis of mitochondria and improved organelle function. Exercise also promotes the degradation of poorly functioning mitochondria (i.e. mitophagy), thereby accelerating mitochondrial turnover, and preserving a pool of healthy organelles. In contrast, muscle disuse, as well as the aging process, are associated with reduced mitochondrial quality and quantity in muscle. This has strong negative implications for whole-body metabolic health and the preservation of muscle mass. A number of traditional, as well as novel regulatory pathways exist in muscle that control both biogenesis and mitophagy. Interestingly, although the ablation of single regulatory transcription factors within these pathways often leads to a reduction in the basal mitochondrial content of muscle, this can invariably be overcome with exercise, signifying that exercise activates a multitude of pathways which can respond to restore mitochondrial health. This knowledge, along with growing realization that pharmacological agents can also promote mitochondrial health independently of exercise, leads to an optimistic outlook in which the maintenance of mitochondrial and whole-body metabolic health can be achieved by taking advantage of the broad benefits of exercise, along with the potential specificity of drug action.
authors.affiliation: Muscle Health Research Centre, School of Kinesiology and Health Science, York University, Toronto, Ontario, Canada M3J 1P3 dhood@yorku.ca.
authors.forename: David A
authors.initials: DA
authors.lastname: Hood
authors.affiliation: Muscle Health Research Centre, School of Kinesiology and Health Science, York University, Toronto, Ontario, Canada M3J 1P3.
authors.forename: Liam D
authors.initials: LD
authors.lastname: Tryon
authors.affiliation: Muscle Health Research Centre, School of Kinesiology and Health Science, York University, Toronto, Ontario, Canada M3J 1P3.
authors.forename: Heather N
authors.initials: HN
authors.lastname: Carter
authors.affiliation: Muscle Health Research Centre, School of Kinesiology and Health Science, York University, Toronto, Ontario, Canada M3J 1P3.
authors.forename: Yuho
authors.initials: Y
authors.lastname: Kim
authors.affiliation: Muscle Health Research Centre, School of Kinesiology and Health Science, York University, Toronto, Ontario, Canada M3J 1P3.
authors.forename: Chris C W
authors.initials: CC
authors.lastname: Chen
mesh_terms: D000375:Aging / Q000378:metabolism; D000818:Animals; D015444:Exercise; D006801:Humans; D008931:Mitochondria, Muscle / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism*; D001678:Organelle Biogenesis; D021381:Protein Transport; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism
chemical_list: D024101:Mitochondrial Proteins; D015534:Trans-Activators
keywords: PPARγ co-activator-1α (PGC-1α); Tfam; Tfeb; aging; calcium signalling; exercise; exercise training; mitochondrial protein import; mitochondrial reticulum; mitophagy; mtDNA; muscle disuse; p53; reactive oxygen species