CBL/CAP is essential for mitochondria respiration complex I assembly and bioenergetics efficiency in muscle cells.

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 my-ocytes 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 signalling to efficient mitochondrial respiratory function and metabolism in muscle.