Raptor is critical for increasing the mitochondrial proteome and skeletal muscle force during hypertrophy.
Animals
Female
Hypertrophy
/ physiopathology
Male
Mechanistic Target of Rapamycin Complex 1
/ metabolism
Mice
Mice, Inbred C57BL
Mice, Knockout
Mitochondria
/ metabolism
Mitochondrial Proteins
/ metabolism
Muscle, Skeletal
/ metabolism
Phosphorylation
Proteome
/ analysis
Regulatory-Associated Protein of mTOR
/ physiology
Signal Transduction
Raptor
hypertrophy
mTOR
mitochondria
rapamycin
skeletal muscle
Journal
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
ISSN: 1530-6860
Titre abrégé: FASEB J
Pays: United States
ID NLM: 8804484
Informations de publication
Date de publication:
12 2021
12 2021
Historique:
revised:
11
10
2021
received:
23
06
2021
accepted:
22
10
2021
entrez:
12
11
2021
pubmed:
13
11
2021
medline:
21
12
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 34767636
doi: 10.1096/fj.202101054RR
doi:
Substances chimiques
Mitochondrial Proteins
0
Proteome
0
Regulatory-Associated Protein of mTOR
0
Rptor protein, mouse
0
Mechanistic Target of Rapamycin Complex 1
EC 2.7.11.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e22031Informations de copyright
© 2021 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.
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