title: The beneficial role of proteolysis in skeletal muscle growth and stress adaptation.
abstract: Muscle atrophy derived from excessive proteolysis is a hallmark of numerous disease conditions. Accordingly, the negative consequences of skeletal muscle protein breakdown often overshadow the critical nature of proteolytic systems in maintaining normal cellular function. Here, we discuss the major cellular proteolysis machinery-the ubiquitin/proteosome system, the autophagy/lysosomal system, and caspase-mediated protein cleavage-and the critical role of these protein machines in establishing and preserving muscle health. We examine how ordered degradation modifies (1) the spatiotemporal expression of myogenic regulatory factors during myoblast differentiation, (2) membrane fusion during myotube formation, (3) sarcomere remodeling and muscle growth following physical stress, and (4) energy homeostasis during nutrient deprivation. Finally, we review the origin and etiology of a number of myopathies and how these devastating conditions arise from inborn errors in proteolysis.
authors.affiliation: Regenerative Medicine Program, Sprott Center for Stem Cell Research, Ottawa Hospital Research Institute, The Ottawa Hospital, Ottawa, ON K1H 8L6 Canada ; Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON Canada.
authors.forename: Ryan A V
authors.initials: RA
authors.lastname: Bell
authors.affiliation: Regenerative Medicine Program, Sprott Center for Stem Cell Research, Ottawa Hospital Research Institute, The Ottawa Hospital, Ottawa, ON K1H 8L6 Canada ; Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON Canada.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Al-Khalaf
authors.affiliation: Regenerative Medicine Program, Sprott Center for Stem Cell Research, Ottawa Hospital Research Institute, The Ottawa Hospital, Ottawa, ON K1H 8L6 Canada ; Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON Canada ; Department of Medicine, Division of Cardiology, University of Ottawa, Ottawa, ON Canada.
authors.forename: Lynn A
authors.initials: LA
authors.lastname: Megeney
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D001343:Autophagy; D020169:Caspases / Q000378:metabolism; D006801:Humans; D008247:Lysosomes / Q000201:enzymology; D024510:Muscle Development; D018482:Muscle, Skeletal / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D009133:Muscular Atrophy / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D010447:Peptide Hydrolases / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D059748:Proteolysis; D012038:Regeneration; D015398:Signal Transduction; D013312:Stress, Physiological; D054875:Ubiquitination
chemical_list: D010447:Peptide Hydrolases; D020169:Caspases; D046988:Proteasome Endopeptidase Complex
keywords: Autophagy; Caspase; Muscle cell differentiation; Muscle growth; Proteasome; Proteolysis