A1 Refereed original research article in a scientific journal

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




AuthorsAye 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

PublisherMDPI

Publication year2023

JournalInternational Journal of Molecular Sciences

Journal name in sourceINTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

Journal acronymINT J MOL SCI

Article number 3399

Volume24

Issue4

Number of pages17

eISSN1422-0067

DOIhttps://doi.org/10.3390/ijms24043399

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

Self-archived copy’s web addresshttps://research.utu.fi/converis/portal/detail/Publication/178964188


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.

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