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
Authors: 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
Publication year: 2023
Journal: International Journal of Molecular Sciences
Journal name in source: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Journal acronym: INT J MOL SCI
Article number: 3399
Volume: 24
Issue: 4
Number of pages: 17
eISSN: 1422-0067
DOI: https://doi.org/10.3390/ijms24043399
Web address : https://doi.org/10.3390/ijms24043399
Self-archived copy’s web address: 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.
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