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- Title
CBL/CAP Is Essential for Mitochondria Respiration Complex I Assembly and Bioenergetics Efficiency in Muscle Cells.
- Authors
Aye, Cho-Cho; Hammond, Dean E.; Rodriguez-Cuenca, Sergio; Doherty, Mary K.; Whitfield, Phillip D.; Phelan, Marie M.; Yang, Chenjing; Perez-Perez, Rafael; Li, Xiaoxin; Diaz-Ramos, Angels; Peddinti, Gopal; Oresic, Matej; Vidal-Puig, Antonio; Zorzano, Antonio; Ugalde, Cristina; Mora, Silvia
- 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.
- Subjects
BIOENERGETICS; MUSCLE cells; MITOCHONDRIA; INSULIN sensitivity; MUSCLE metabolism; PLANT mitochondria; INSULIN receptors; RESPIRATION
- Publication
International Journal of Molecular Sciences, 2023, Vol 24, Issue 4, p3399
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms24043399