Baraldo, Martina, Nogara, Leonardo, Dumitras, Georgia Ana, Tchampda Dondjang, Achille Homere, Geremia, Alessia, Scalabrin, Marco, Turk, Clara, Telkamp, Frederik, Zentilin, Lorena, Giacca, Mauro, Kruger, Marcus and Blaauw, Bert (2021). Raptor is critical for increasing the mitochondrial proteome and skeletal muscle force during hypertrophy. Faseb J., 35 (12). HOBOKEN: WILEY. ISSN 1530-6860

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Abstract

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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Baraldo, MartinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nogara, LeonardoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dumitras, Georgia AnaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tchampda Dondjang, Achille HomereUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Geremia, AlessiaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Scalabrin, MarcoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Turk, ClaraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Telkamp, FrederikUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zentilin, LorenaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Giacca, MauroUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kruger, MarcusUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Blaauw, BertUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-592882
DOI: 10.1096/fj.202101054RR
Journal or Publication Title: Faseb J.
Volume: 35
Number: 12
Date: 2021
Publisher: WILEY
Place of Publication: HOBOKEN
ISSN: 1530-6860
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
PATHWAY; GROWTH; REGENERATION; ABLATION; RICTOR; 4E-BP1Multiple languages
Biochemistry & Molecular Biology; Biology; Cell BiologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/59288

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