title: Disrupted autophagy undermines skeletal muscle adaptation and integrity.
abstract: This review assesses the importance of proteostasis in skeletal muscle maintenance with a specific emphasis on autophagy. Skeletal muscle appears to be particularly vulnerable to genetic defects in basal and induced autophagy, indicating that autophagy is co-substantial to skeletal muscle maintenance and adaptation. We discuss emerging evidence that tension-induced protein unfolding may act as a direct link between mechanical stress and autophagic pathways. Mechanistic links between protein damage, autophagy and muscle hypertrophy, which is also induced by mechanical stress, are still poorly understood. However, some mouse models of muscle disease show ameliorated symptoms upon effective targeting of basal autophagy. These findings highlight the importance of autophagy as therapeutic target and suggest that elucidating connections between protein unfolding and mTOR-dependent or mTOR-independent hypertrophic responses is likely to reveal specific therapeutic windows for the treatment of muscle wasting disorders.
authors.affiliation: Department of Biology, University of York, Wentworth Way, York, YO10 5DD, UK.
authors.forename: Elliot J
authors.initials: EJ
authors.lastname: Jokl
authors.affiliation: Department of Biology, University of York, Wentworth Way, York, YO10 5DD, UK. gonzalo.blanco@york.ac.uk.
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Blanco
mesh_terms: D000222:Adaptation, Physiological / Q000235:genetics; D000818:Animals; D001343:Autophagy / Q000235:genetics*; D006801:Humans; D006984:Hypertrophy / Q000235:genetics* / Q000503:physiopathology; D051379:Mice; D018482:Muscle, Skeletal / Q000473:pathology / Q000502:physiology*; D009135:Muscular Diseases / Q000235:genetics* / Q000503:physiopathology; D058767:Protein Unfolding; D000074702:Proteostasis / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D013314:Stress, Mechanical; D058570:TOR Serine-Threonine Kinases / Q000235:genetics*
chemical_list: C546843:mTOR protein, mouse; D058570:TOR Serine-Threonine Kinases