Raptor is critical for increasing the mitochondrial proteome and skeletal muscle force during hypertrophy

TY - JOUR

T1 - Raptor is critical for increasing the mitochondrial proteome and skeletal muscle force during hypertrophy

AU - Baraldo, Martina

AU - Nogara, Leonardo

AU - Dumitras, Georgia Ana

AU - Tchampda Dondjang, Achille Homère

AU - Geremia, Alessia

AU - Scalabrin, Marco

AU - Türk, Clara

AU - Telkamp, Frederik

AU - Zentilin, Lorena

AU - Giacca, Mauro

AU - Krüger, Marcus

AU - Blaauw, Bert

N1 - Funding Information: This work was supported by grants from Association Française contre les Myopathies (AFMTéléthon to B.B., no. 21865), University of Padova (STARS‐MyoAktivation to B.B.), Associazione Italiana per la Ricerca sul Cancro (AIRC)‐20406 to B.B. We would like to thank Sabrina Zorzato for help during the revision process. Publisher Copyright: © 2021 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.

PY - 2021/12

Y1 - 2021/12

N2 - Loss of skeletal muscle mass and force is of critical importance in numerous pathologies, like age-related sarcopenia or cancer. It has been shown that the Akt-mTORC1 pathway is critical for stimulating adult muscle mass and function, however, it is unknown if mTORC1 is the only mediator downstream of Akt and which intracellular processes are required for functional muscle growth. Here, we show that loss of Raptor reduces muscle hypertrophy after Akt activation and completely prevents increases in muscle force. Interestingly, the residual hypertrophy after Raptor deletion can be completely prevented by administration of the mTORC1 inhibitor rapamycin. Using a quantitative proteomics approach we find that loss of Raptor affects the increases in mitochondrial proteins, while rapamycin mainly affects ribosomal proteins. Taken together, these results suggest that mTORC1 is the key mediator of Akt-dependent muscle growth and its regulation of the mitochondrial proteome is critical for increasing muscle force.

AB - Loss of skeletal muscle mass and force is of critical importance in numerous pathologies, like age-related sarcopenia or cancer. It has been shown that the Akt-mTORC1 pathway is critical for stimulating adult muscle mass and function, however, it is unknown if mTORC1 is the only mediator downstream of Akt and which intracellular processes are required for functional muscle growth. Here, we show that loss of Raptor reduces muscle hypertrophy after Akt activation and completely prevents increases in muscle force. Interestingly, the residual hypertrophy after Raptor deletion can be completely prevented by administration of the mTORC1 inhibitor rapamycin. Using a quantitative proteomics approach we find that loss of Raptor affects the increases in mitochondrial proteins, while rapamycin mainly affects ribosomal proteins. Taken together, these results suggest that mTORC1 is the key mediator of Akt-dependent muscle growth and its regulation of the mitochondrial proteome is critical for increasing muscle force.

KW - hypertrophy

KW - mitochondria

KW - mTOR

KW - rapamycin

KW - Raptor

KW - skeletal muscle

UR - http://www.scopus.com/inward/record.url?scp=85120699435&partnerID=8YFLogxK

U2 - 10.1096/fj.202101054RR

DO - 10.1096/fj.202101054RR

M3 - Article

AN - SCOPUS:85120699435

SN - 0892-6638

VL - 35

JO - Faseb Journal

JF - Faseb Journal

IS - 12

M1 - e22031

ER -