CBL/CAP is essential for mitochondria respiration complex I assembly and bioenergetics efficiency in muscle cells

Aye, C.-C. et al. (2023) CBL/CAP is essential for mitochondria respiration complex I assembly and bioenergetics efficiency in muscle cells. International Journal of Molecular Sciences, 24(4), 3399. (doi: 10.3390/ijms24043399) (PMID:36834818) (PMCID:PMC9964740)

Abstract

CBL is rapidly phosphorylated upon insulin receptor activation. Mice whole body CBL depletion improved insulin sensitivity and glucose clearance; however, the precise mechanisms remain unknown. We depleted either CBL or its associated protein SORBS1/CAP independently in myocytes and assessed mitochondrial function and metabolism compared to control cells. CBL- and CAP-depleted cells showed increased mitochondrial mass with greater proton leak. Mitochondrial respiratory complex I activity and assembly into respirasomes were reduced. Proteome profiling revealed alterations in proteins involved in glycolysis and fatty acid degradation. Our findings demonstrate CBL/CAP pathway couples insulin signaling to efficient mitochondrial respiratory function and metabolism in muscle.

• Item Type: Articles
• Additional Information: This work was supported by the University of Liverpool, a research grant from the European Commission (Framework 7 grant HEALTH-F4-2008-223450 to S.M., A.Z., A.V.-P., M.O.), by National Institute of Health RO1 grant GM105781 (to C.U.) and by Instituto de Salud Carlos III-MINECO/European FEDER Funds grant PI17-00048 (to C.U.). M.K.D. and P.D.W. acknowledge funding from European Regional Development Fund, Scottish Funding Council and Highlands and Islands Enterprise.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Whitfield, Professor Phil
• Authors: Aye, C.-C., Hammond, D. E., Rodriguez-Cuenca, S., Doherty, M. K., Whitfield, P. D., Phelan, M. M., Yang, C., Perez-Perez, R., Li, X., Diaz-Ramos, A., Peddinti, G., Oresic, M., Vidal-Puig, A., Zorzano, A., Ugalde, C., and Mora, S.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: International Journal of Molecular Sciences
• Publisher: MDPI
• ISSN: 1661-6596
• ISSN (Online): 1422-0067
• Copyright Holders: Copyright © 2023 The Authors
• First Published: First published in International Journal of Molecular Sciences 24(4):3399
• Publisher Policy: Reproduced under a Creative Commons License