Regulation of Myogenic Cell Apoptosis, UPS, and Autophagy During Mammalian Skeletal Myogenesis

Skeletal myogenesis is an extremely complex process that mononuclear myoblasts undergo proliferation, differentiation, and fusion to form multinucleated contractile muscle fibers, involving a balance between synthesis and degradation metabolism. Skeletal muscle requires an effective mechanism to balance rapid proliferation by degrading supernumerary or damaged organelles/proteins, or by activating cellular signals to regulate subsequent muscle differentiation. In recent years, three important cellular processes—apoptosis, ubiquitin–proteasome system (UPS), and autophagy—have received extensive attention in skeletal myogenesis. The UPS supports the early differentiation process and initiates apoptosis, and the increase in apoptosis activates autophagy to clear damaged organelles and proteins, which in turn inhibits apoptosis, preventing excessive cell death and maintaining cellular stability. The coordination among apoptosis, UPS, and autophagy is more intricate, as they interact through a dynamic balancing mechanism, determining the balance between cell death and survival, and enabling proper muscle differentiation. Here, we explore the molecular signals that mediate apoptosis, UPS, and autophagy, with a focus on analyzing their interrelationship in skeletal myogenesis. Studying the regulatory mechanisms of these molecules will help in understanding the role of cell death in skeletal muscle development, especially how they affect muscle cell differentiation, providing new insights into mammalian skeletal myogenesis.