Institute of Biochemistry and Molecular Biology, ZBMZ, Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany; Faculty of Biology, University of Freiburg, 79104 Freiburg, Germany.
Institute of Biochemistry and Molecular Biology, ZBMZ, Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany.
Mol Cell. 2019 Mar 7;73(5):1056-1065.e7. doi: 10.1016/j.molcel.2018.12.014. Epub 2019 Feb 6.
The mitochondrial inner membrane harbors a large number of metabolite carriers. The precursors of carrier proteins are synthesized in the cytosol and imported into mitochondria by the translocase of the outer membrane (TOM) and the carrier translocase of the inner membrane (TIM22). Molecular chaperones in the cytosol and intermembrane space bind to the hydrophobic precursors to prevent their aggregation. We report that the major metabolite channel of the outer membrane, termed porin or voltage-dependent anion channel (VDAC), promotes efficient import of carrier precursors. Porin interacts with carrier precursors arriving in the intermembrane space and recruits TIM22 complexes, thus ensuring an efficient transfer of the precursors to the inner membrane translocase. Porin channel mutants impaired in metabolite transport are not disturbed in carrier import into mitochondria. We conclude that porin serves distinct functions as outer membrane channel for metabolites and as coupling factor for protein translocation into the inner membrane.
线粒体的内膜中含有大量的代谢物载体。载体蛋白的前体在细胞质中合成，并通过外膜转位酶（TOM）和内膜载体转位酶（TIM22）进入线粒体。细胞质和膜间空间中的分子伴侣与疏水的前体结合，以防止其聚集。我们报告称，外膜的主要代谢物通道，称为孔蛋白或电压依赖性阴离子通道（VDAC），可促进载体前体的有效导入。孔蛋白与到达膜间空间的载体前体相互作用，并募集 TIM22 复合物，从而确保前体有效地转移到内膜转位酶。在代谢物转运中存在功能缺陷的孔蛋白突变体不会干扰载体向线粒体的导入。我们的结论是，孔蛋白作为外膜代谢物通道和蛋白质向内膜转运的偶联因子具有不同的功能。
