Identification and functional analysis of novel interacting proteins for regulation of mitochondrial c-Src activity

非受体型酪氨酸激酶c-Src参与基本细胞功能，包括增殖、分化和存活。最近的研究表明，c-Src也存在于线粒体中，并参与线粒体能量产生的调节机制。在这里，我们已经确定了新的相互作用蛋白质与c-Src在线粒体中，并研究其功能的c-Src激酶活性的调节。血清饥饿显示呼吸和线粒体c-Src活性的显着降低，并在人类T98 G细胞的活性氧产生的增强。蛋白质组分析显示线粒体c-Src相互作用蛋白包括呼吸复合体V的ATP 5A 1。ATP 5A 1在细胞中的过表达表现出c-Src激酶活性和线粒体呼吸的显着增加。这些结果表明，ATP 5A 1通过与线粒体中的c-Src复合物相互作用来调节c-Src激酶活性，并且它们的相互作用对于细胞呼吸是必需的。

Non-receptor-type tyrosine kinase c-Src is implicated in fundamental cellular functions including proliferation, differentiation and survival. Recent studies have suggested that c-Src is also present in mitochondria and involved in the regulatory mechanisms of mitochondrial energy production. Here we have identified novel interaction proteins with c-Src in mitochondria, and investigated their function in the regulation of c-Src kinase activity. Serum starvation exhibits significant reductions of respiration and mitochondrial c-Src activity, and an enhancement of reactive oxygen species production in human T98G cells. Proteome analysis reveals mitochondrial c-Srcinteraction proteins including ATP5A1 of respiratory complex V. Overexpression of ATP5A1 in cells exhibits a significant increase in c-Src kinase activity and respiration in mitochondria. These results suggest that ATP5A1 regulates c-Src kinase activity by its interaction with c-Src complex in mitochondria, and that their interaction is essential for cellular respiration.