Transcriptional regulation of autophagy in skeletal muscle stem cells

ABSTRACT

Muscle stem cells (MuSCs) are essential for the regenerative capabilities of skeletal muscles. MuSCs are maintained in a quiescent state, but, when activated, can undergo proliferation and differentiation into myocytes, which fuse and mature to generate muscle fibers. The maintenance of MuSC quiescence and MuSC activation are processes that are tightly regulated by autophagy, a conserved degradation system that removes unessential or dysfunctional cellular components via lysosomes. Both the upregulation and downregulation of autophagy have been linked to impaired muscle regeneration, causing myopathies such as cancer cachexia, sarcopenia and Duchenne muscular dystrophy. In this Review, we highlight the importance of autophagy in regulating MuSC activity during muscle regeneration. Additionally, we summarize recent studies that link the transcriptional dysregulation of autophagy to muscle atrophy, emphasizing the dominant roles that transcription factors play in myogenic programs. Deciphering and understanding the roles of these transcription factors in the regulation of autophagy during myogenesis could advance the development of regenerative medicine.

Abstract

Summary: This Review highlights recent studies linking transcriptional dysregulation of autophagy to muscle stem cell dysfunction. A deeper understanding of autophagy regulation in muscle stem cells could facilitate the development of regenerative therapies for muscle atrophy-related diseases.