CBL/CAP Is Essential for Mitochondria Respiration Complex I Assembly and Bioenergetics Efficiency in Muscle Cells

Aye, CC, Hammond, DE ORCID: 0000-0002-6326-8739, Rodriguez-Cuenca, S ORCID: 0000-0001-9635-0504, Doherty, MK ORCID: 0000-0002-3480-4088, Whitfield, PD, Phelan, MM, Yang, C, Perez-Perez, R, Li, X, Diaz-Ramos, A, Peddinti, G ORCID: 0000-0002-8767-968X, Oresic, M, Vidal-Puig, A, Zorzano, A, Ugalde, C ORCID: 0000-0002-9742-1877 and Mora, S ORCID: 0000-0002-8473-1497 (2023) CBL/CAP Is Essential for Mitochondria Respiration Complex I Assembly and Bioenergetics Efficiency in Muscle Cells. International Journal of Molecular Sciences, 24 (4). ISSN 1661-6596

Preview

Text CBLCAP Is Essential for Mitochondria Respiration Complex I Assembly and Bioenergetics Efficiency in Muscle Cells.pdf - Published Version Available under License Creative Commons Attribution. Download (2MB) | Preview

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:	Article
Uncontrolled Keywords:	Mitochondria; Mitochondria, Muscle; Muscle Cells; Animals; Mice; Insulin Resistance; Microfilament Proteins; Insulin; Cell Respiration; Energy Metabolism; Proto-Oncogene Proteins c-cbl; CBL; SORBS1; glucose transport; insulin resistance; insulin signalling; mitochondria; Animals; Mice; Energy Metabolism; Insulin; Insulin Resistance; Mitochondria; Mitochondria, Muscle; Muscle Cells; Proto-Oncogene Proteins c-cbl; Cell Respiration; Microfilament Proteins; 3101 Biochemistry and Cell Biology; 31 Biological Sciences; Lung; Diabetes; 2.1 Biological and endogenous factors; 1.1 Normal biological development and functioning; Animals; Mice; Energy Metabolism; Insulin; Insulin Resistance; Mitochondria; Mitochondria, Muscle; Muscle Cells; Proto-Oncogene Proteins c-cbl; Cell Respiration; Microfilament Proteins; 0399 Other Chemical Sciences; 0604 Genetics; 0699 Other Biological Sciences; Chemical Physics; 3101 Biochemistry and cell biology; 3107 Microbiology; 3404 Medicinal and biomolecular chemistry
Subjects:	Q Science > QH Natural history > QH301 Biology Q Science > QM Human anatomy
Divisions:	Pharmacy and Biomolecular Sciences
Publisher:	MDPI
Date of acceptance:	4 February 2023
Date of first compliant Open Access:	7 July 2026
Date Deposited:	07 Jul 2026 10:01
Last Modified:	07 Jul 2026 10:01
DOI or ID number:	10.3390/ijms24043399
URI:	https://researchonline.ljmu.ac.uk/id/eprint/28965

View Item