mTORC1 mediates fiber type-specific regulation of protein synthesis and muscle size during denervation

• Main Authors: Jae-Sung You, Kookjoo Kim, Nathaniel D. Steinert, Jie Chen, Troy A. Hornberger
• Format: Article
• Language: English
• Published: Nature Publishing Group 2021-04-01
• Series: Cell Death Discovery
• Online Access: https://doi.org/10.1038/s41420-021-00460-w

Abstract Skeletal muscle denervation occurs in diverse conditions and causes severe muscle atrophy. Signaling by mammalian target of rapamycin complex 1 (mTORC1) plays a central role in the maintenance of skeletal muscle mass by regulating net protein balance; yet, its role in denervation-induced atrophy is unclear. In this study, by using skeletal muscle-specific and inducible raptor knockout mice, we demonstrate that signaling through mTORC1 is activated during denervation and plays an essential role in mitigating the atrophy of non-type IIB muscle fibers. Measurements of protein synthesis rates of individual fibers suggest that denervation increases protein synthesis specifically in non-type IIB muscle fibers and that mTORC1 is required for this event. Furthermore, denervation induced a more pronounced increase in the level of phosphorylated ribosomal S6 protein in non-type IIB muscle fibers than in type IIB muscle fibers. Collectively, our results unveil a novel role for mTORC1 in mediating a fiber type-specific regulation of muscle size and protein synthesis during denervation.