The beneficial role of proteolysis in skeletal muscle growth and stress adaptation

Skelet Muscle. 2016 Apr 6:6:16. doi: 10.1186/s13395-016-0086-6. eCollection 2016.


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.

Keywords: Autophagy; Caspase; Muscle cell differentiation; Muscle growth; Proteasome; Proteolysis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adaptation, Physiological
  • Animals
  • Autophagy
  • Caspases / metabolism
  • Humans
  • Lysosomes / enzymology
  • Muscle Development*
  • Muscle, Skeletal / enzymology*
  • Muscle, Skeletal / pathology
  • Muscle, Skeletal / physiopathology
  • Muscular Atrophy / enzymology*
  • Muscular Atrophy / pathology
  • Muscular Atrophy / physiopathology
  • Peptide Hydrolases / metabolism*
  • Proteasome Endopeptidase Complex / metabolism
  • Proteolysis*
  • Regeneration*
  • Signal Transduction
  • Stress, Physiological*
  • Ubiquitination


  • Peptide Hydrolases
  • Caspases
  • Proteasome Endopeptidase Complex