Regulation of skeletal muscle proteolysis by amino acids

Skeletal muscle is the major reservoir of body protein that can be mobilized in a number of muscle wasting conditions, that include kidney failure. Increased proteolysis in such conditions provides free amino acids that are used for acute-phase protein synthesis or that are degraded for energy purposes. Amino acids act as signals to regulate both protein synthesis and protein breakdown. We review the current but limited information available on the regulation of proteolytic systems in muscle cells. In particular, recent data have shown that amino acid deprivation in C2C12 myotubes stimulates autophagic sequestration by mechanisms that implicate the Apg system through a class III phosphoinositide-3′-kinase (PI3KIII) signaling cascade.