Role of the ubiquitin-proteasome pathway in skeletal muscle

Skeletal muscle is a plastic organ that is maintained by multiple pathways regulating cell and protein turnover. The ubiquitin-proteasome system (UPS) is now recognized as a major intracellular degradation system, and its proper function is critical to health and muscle homeostasis. Alterations in muscle proteasomes have been linked to several pathological phenotypes. Indeed, excessive or defective activity of UPS leads to detrimental effects on muscle homeostasis. Emerging evidence suggests that UPS can specifically target proteins that govern pathological signaling pathways for degradation, thus altering downstream effectors and disease outcomes. An increasing number of studies link abnormalities in the regulation of UPS to myofiber degeneration and muscle weakness. Therefore, an understanding of the pathogenic role of the proteostatic system in each inherited muscle disorder may provide novel therapeutic targets to counteract muscle wasting. In this section, we focus on the function of the proteasome system with respect to several diseases with altered proteostasis.