CBL/CAP Is Essential for Mitochondria Respiration Complex I Assembly and Bioenergetics Efficiency in Muscle Cells.
CBL/CAP Is Essential for Mitochondria Respiration Complex I Assembly and Bioenergetics Efficiency in Muscle Cells.
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DOI：
10.3390/ijms24043399
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发表时间：
2023-02-08
影响因子：
5.6
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中科院分区：
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CBL在胰岛素受体活化后迅速磷酸化。小鼠全身CBL消耗改善胰岛素敏感性和葡萄糖清除率;然而，确切的机制仍然未知。我们在心肌细胞中独立地耗尽CBL或其相关蛋白SORBS 1/CAP，并与对照细胞相比评估线粒体功能和代谢。CBL-和CAP-耗尽的细胞显示线粒体质量增加，质子泄漏更大。线粒体呼吸复合物I活性和组装成线粒体酶体减少。蛋白质组分析显示糖酵解和脂肪酸降解蛋白质的改变。我们的研究结果表明，CBL/CAP途径耦合胰岛素信号，有效的线粒体呼吸功能和代谢的肌肉。
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.