TY - JOUR
T1 - mTORC1 mediates fiber type-specific regulation of protein synthesis and muscle size during denervation
AU - You, Jae Sung
AU - Kim, Kookjoo
AU - Steinert, Nathaniel D.
AU - Chen, Jie
AU - Hornberger, Troy A.
N1 - Funding Information:
This work was supported by the National Institutes of Health, National Institute of Arthritis and Musculoskeletal and Skin Diseases Grants to T.A.H. (AR057347 and AR074932) and J.C. (AR048914), and National Institute of General Medical Sciences Grant to J.C. (GM089771).
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/6
Y1 - 2021/6
N2 - 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.
AB - 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.
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U2 - 10.1038/s41420-021-00460-w
DO - 10.1038/s41420-021-00460-w
M3 - Article
C2 - 33846288
SN - 2058-7716
VL - 7
JO - Cell Death Discovery
JF - Cell Death Discovery
IS - 1
M1 - 74
ER -