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



: Aye Cho-Cho, Hammond Dean E, Rodriguez-Cuenca Sergio, Doherty Mary K, Whitfield Phillip D, Phelan Marie M, Yang Chenjing J, Perez-Perez Rafael, Li Xiaoxin, Diaz-Ramos Angels, Peddinti Gopal, Oresic Matej, Vidal-Puig Antonio, Zorzano Antonio, Ugalde Cristina, Mora Silvia

Publisher: MDPI

: 2023

: International Journal of Molecular Sciences

: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

: INT J MOL SCI

:  3399

: 24

: 4

: 17

: 1422-0067

DOI: https://doi.org/10.3390/ijms24043399

: https://doi.org/10.3390/ijms24043399

: https://research.utu.fi/converis/portal/detail/Publication/178964188


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.

Last updated on 2024-26-11 at 10:59