The Importance of mTORC1-Autophagy Axis for Skeletal Muscle Diseases

Abstract

The mechanistic target of rapamycin (mTOR) complex 1, mTORC1, integrates nutrient and growth factor signals with cellular responses and plays critical roles in regulating cell growth, proliferation, and lifespan. mTORC1 signaling has been reported as a central regulator of autophagy by modulating almost all aspects of the autophagic process, including initiation, expansion, and termination. An increasing number of studies suggest that mTORC1 and autophagy are critical for the physiological function of skeletal muscle and are involved in diverse muscle diseases. Here, we review recent insights into the essential roles of mTORC1 and autophagy in skeletal muscles and their implications in human muscle diseases. Multiple inhibitors targeting mTORC1 or autophagy have already been clinically approved, while others are under development. These chemical modulators that target the mTORC1/autophagy pathways represent promising potentials to cure muscle diseases.

Keywords: autophagy; mTORC1; muscle diseases.

Figure 1

A schematic representation of mTOR complexes.

Figure 2

Regulation of autophagy by mTORC1. mTORC1 plays critical roles in the regulation of each step of the autophagy procedure, including autophagy initiation, nucleation, membrane expansion, and termination.

Figure 3

Protein homeostasis is regulated by the mTORC1-autophagy axis in muscles.

Figure 4

A schematic representation of muscle regeneration. Muscle stem cells (MuSCs) activation, proliferation, differentiation into myoblasts and fusion of myoblasts to form myofibers are under the regulation of mTORC1 signaling and autophagy.