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

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

Tutkimustuotos: LehtiartikkeliArtikkeliTieteellinenvertaisarvioitu

1 Sitaatiot (Scopus)
11 Lataukset (Pure)

Abstrakti

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.

AlkuperäiskieliEnglanti
JulkaisuInternational Journal of Molecular Sciences
Vuosikerta24
Numero4
DOI - pysyväislinkit
TilaJulkaistu - 8 helmik. 2023
OKM-julkaisutyyppiA1 Julkaistu artikkeli, soviteltu

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