Muscle inactivity activates four proteolytic systems that mediate protein degradation: 1) caspase-3; 2) calpain; 3) Autophagy; 4) and the ubiquitin proteasome system (UBS). Additionally, prolonged muscle inactivity results in the inhibition of the PI3K/Akt/mTOR pathway which mediates protein synthesis. See text for more details. FoxO, forkhead box O; MuRF-1, muscle ring finger protein-1; LC3, microtubule-associated proteins 1A/1B light chain 3b; Bnip3, BCL2 interacting protein 3; PI3K, phosphatidylinositol 3-kinase; Akt, protein kinase B; mTOR, mammalian/mechanistic target of rapamycin.