Faculty of Life Sciences, Kyoto Sangyo University, Kamigamo-motoyama, Kita-ku, Kyoto 603-8555, Japan; Institute for Protein Dynamics, Kyoto Sangyo University, Kamigamo-motoyama, Kita-ku, Kyoto 603-8555, Japan.
Organization for Promotion of Tenure Track, University of Miyazaki, 1-1 Gakuenkibanadai-nishi, Miyazaki 889-2192, Japan; Infection and Immunity Program, Biomedicine Discovery Institute and Department of Microbiology, Monash University, Melbourne 3800, Australia.
Mol Cell. 2019 Mar 7;73(5):1044-1055.e8. doi: 10.1016/j.molcel.2019.01.003. Epub 2019 Feb 6.
Mitochondria import nearly all of their resident proteins from the cytosol, and the TOM complex functions as their entry gate. The TOM complex undergoes a dynamic conversion between the majority population of a three-channel gateway ("trimer") and the minor population that lacks Tom22 and has only two Tom40 channels ("dimer"). Here, we found that the porin Por1 acts as a sink to bind newly imported Tom22. This Por1 association thereby modulates Tom22 integration into the TOM complex, guaranteeing formation of the functional trimeric TOM complex. Por1 sequestration of Tom22 dissociated from the trimeric TOM complex also enhances the dimeric TOM complex, which is preferable for the import of TIM40/MIA-dependent proteins into mitochondria. Furthermore, Por1 appears to contribute to cell-cycle-dependent variation of the functional trimeric TOM complex by chaperoning monomeric Tom22, which arises from the cell-cycle-controlled variation of phosphorylated Tom6.
线粒体从细胞质中几乎导入所有其驻留蛋白，而 TOM 复合物作为其进入的入口。TOM 复合物在多数的三通道门（“三聚体”）和缺少 Tom22 且仅有两个 Tom40 通道的少数群体（“二聚体”）之间进行动态转换。在这里，我们发现孔蛋白 Por1 作为结合新导入的 Tom22 的汇来发挥作用。Por1 与 Tom22 的这种结合从而调节 Tom22 整合到 TOM 复合物中，保证了功能性三聚体 TOM 复合物的形成。从三聚体 TOM 复合物中分离出来的 Tom22 与 Por1 的结合也增强了二聚体 TOM 复合物，这有利于 TIM40/MIA 依赖性蛋白导入线粒体。此外，Por1 似乎通过伴侣蛋白来促使单体 Tom22 发挥作用，从而对功能性三聚体 TOM 复合物的细胞周期依赖性变化做出贡献，Tom22 是由磷酸化 Tom6 的细胞周期控制变化引起的。
