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 (Corresponding Author)

Research output: Contribution to journalArticleScientificpeer-review

1 Citation (Scopus)


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.

Original languageEnglish
Article number3399
Number of pages17
JournalInternational Journal of Molecular Sciences
Issue number4
Publication statusPublished - Feb 2023
MoE publication typeA1 Journal article-refereed


  • CBL
  • glucose transport
  • insulin resistance
  • insulin signalling
  • mitochondria
  • SORBS1
  • Mitochondria, Muscle/metabolism
  • Muscle Cells/metabolism
  • Mitochondria/metabolism
  • Insulin Resistance
  • Animals
  • Proto-Oncogene Proteins c-cbl/metabolism
  • Energy Metabolism
  • Cell Respiration
  • Insulin/metabolism
  • Mice


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