Institut für Biochemie und Molekularbiologie, ZBMZ, Universität Freiburg, 79104 Freiburg, Germany; Trinationales Graduiertenkolleg 1478, Universität Freiburg, 79104 Freiburg, Germany; Faculty of Biology, Universität Freiburg, 79104 Freiburg, Germany.
Cell Metab. 2013 Oct 1;18(4):578-87. doi: 10.1016/j.cmet.2013.09.006.
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.
大多数线粒体蛋白都是通过外膜转位酶（TOM）导入的。Tom22 作为中心受体，将前体蛋白转移到导入孔。酪蛋白激酶 2（CK2）在细胞质前体 Tom22 的 Ser44 和 Ser46 上持续磷酸化，从而促进其导入。目前尚不清楚 Tom22 是否在不同的代谢条件下受到调节。我们报告称，参与葡萄糖诱导的信号转导的 CK1 与线粒体结合。CK1 在 Thr57 处磷酸化 Tom22，并刺激 Tom22 和 Tom20 的组装。相比之下，蛋白激酶 A（PKA）也可被葡萄糖的添加激活，它在 Thr76 处磷酸化 Tom22 的前体，并损害其导入。因此，PKA 的作用与 CK1 和 CK2 相反。我们的结果表明，三种激酶调节 Tom22 的导入和组装，表明中心受体是线粒体蛋白导入的翻译后调节的主要靶标。
