Glucose-Induced Regulation of Protein Import Receptor Tom22 by Cytosolic and Mitochondria-Bound Kinases
Glucose-Induced Regulation of Protein Import Receptor Tom22 by Cytosolic and Mitochondria-Bound Kinases
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DOI：
10.1016/j.cmet.2013.09.006
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发表时间：
2013-10-01
期刊：
影响因子：
29
通讯作者：
Meisinger, Chris
中科院分区：
文献类型：
--
作者：
Gerbeth, Carolin;Schmidt, Oliver;Meisinger, Chris
大多数线粒体蛋白质通过线粒体外膜（TOM）的移位酶输入。Tom22作为中心受体发挥作用，并将前蛋白转移到输入孔。酪蛋白激酶2（CK2）组成型磷酸化Tom22的胞质前体Ser44和Ser46，从而促进其输入。目前尚不清楚Tom22是否在不同的代谢条件下受到调节。我们报告说，CK1，这是参与葡萄糖诱导的信号转导，结合到线粒体。CK1在Thr57磷酸化Tom22并刺激Tom22和Tom20的组装。相比之下，蛋白激酶A（PKA），这也是通过添加葡萄糖激活，磷酸化的前体Tom22在Thr76和削弱其输入。因此，PKA以与CK1和CK2相反的方式起作用。我们的研究结果表明，三种激酶调节Tom22的进口和组装，表明中央受体是线粒体蛋白进口的翻译后调节的主要目标。
Most mitochondrial proteins are imported by the translocase of the outer mitochondrial membrane (TOM). Tom22 functions as central receptor and transfers preproteins to the import pore. Casein kinase 2 (CK2) constitutively phosphorylates the cytosolic precursor of Tom22 at Ser44 and Ser46 and, thus, promotes its import. It is unknown whether Tom22 is regulated under different metabolic conditions. We report that CK1, which is involved in glucose-induced signal transduction, is bound to mitochondria. CK1 phosphorylates Tom22 at Thr57 and stimulates the assembly of Tom22 and Tom20. In contrast, protein kinase A (PKA), which is also activated by the addition of glucose, phosphorylates the precursor of Tom22 at Thr76 and impairs its import. Thus, PKA functions in an opposite manner to CK1 and CK2. Our results reveal that three kinases regulate the import and assembly of Tom22, demonstrating that the central receptor is a major target for the posttranslational regulation of mitochondrial protein import.