Regulation of Mitochondrial Protein Import by Cytosolic Kinases
Regulation of Mitochondrial Protein Import by Cytosolic Kinases
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DOI：
10.1016/j.cell.2010.12.015
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发表时间：
2011-01-21
期刊：
影响因子：
64.5
通讯作者：
Meisinger, Chris
中科院分区：
文献类型：
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作者：
Schmidt, Oliver;Harbauer, Angelika B.;Meisinger, Chris
线粒体通过膜结合运输机制输入大量核编码蛋白，然而，对前蛋白转位酶的调控知之甚少。我们报告，线粒体的主要蛋白质入口门，外膜的转位酶（TOM复合物），被胞质激酶磷酸化，特别是酪蛋白激酶2（CK2）和蛋白激酶A（PKA）。CK2通过两个关键组分的磷酸化促进TOM复合物的生物合成，所述两个关键组分是受体Tom22和输入蛋白Mim 1，这又是进一步输入Tom蛋白所需的。CK2的失活降低了TOM复合物的水平，从而降低了线粒体蛋白质的输入。PKA在非呼吸条件下磷酸化Tom70，从而抑制其受体活性和线粒体代谢物载体的输入。我们的结论是，胞浆激酶发挥刺激和抑制作用的生物合成和功能的TOM复合物，从而调节蛋白质输入到线粒体。
Mitochondria import a large number of nuclear-encoded proteins via membrane-bound transport machineries; however, little is known about regulation of the preprotein translocases. We report that the main protein entry gate of mitochondria, the translocase of the outer membrane (TOM complex), is phosphorylated by cytosolic kinases-in particular, casein kinase 2 (CK2) and protein kinase A (PKA). CK2 promotes biogenesis of the TOM complex by phosphorylation of two key components, the receptor Tom22 and the import protein Mim1, which in turn are required for import of further Tom proteins. Inactivation of CK2 decreases the levels of the TOM complex and thus mitochondrial protein import. PKA phosphorylates Tom70 under nonrespiring conditions, thereby inhibiting its receptor activity and the import of mitochondrial metabolite carriers. We conclude that cytosolic kinases exert stimulatory and inhibitory effects on biogenesis and function of the TOM complex and thus regulate protein import into mitochondria.