Institut für Biochemie und Molekularbiologie, ZBMZ, Universität Freiburg, 79104 Freiburg, Germany.
Mol Biol Cell. 2012 Oct;23(20):3948-56. doi: 10.1091/mbc.E12-04-0295. Epub 2012 Aug 23.
Mitochondria contain two membranes, the outer membrane and the inner membrane with folded cristae. The mitochondrial inner membrane organizing system (MINOS) is a large protein complex required for maintaining inner membrane architecture. MINOS interacts with both preprotein transport machineries of the outer membrane, the translocase of the outer membrane (TOM) and the sorting and assembly machinery (SAM). It is unknown, however, whether MINOS plays a role in the biogenesis of outer membrane proteins. We have dissected the interaction of MINOS with TOM and SAM and report that MINOS binds to both translocases independently. MINOS binds to the SAM complex via the conserved polypeptide transport-associated domain of Sam50. Mitochondria lacking mitofilin, the large core subunit of MINOS, are impaired in the biogenesis of β-barrel proteins of the outer membrane, whereas mutant mitochondria lacking any of the other five MINOS subunits import β-barrel proteins in a manner similar to wild-type mitochondria. We show that mitofilin is required at an early stage of β-barrel biogenesis that includes the initial translocation through the TOM complex. We conclude that MINOS interacts with TOM and SAM independently and that the core subunit mitofilin is involved in biogenesis of outer membrane β-barrel proteins.
线粒体含有两层膜，外膜和具有折叠嵴的内膜。线粒体内膜组织系统 (MINOS) 是维持内膜结构所必需的大型蛋白质复合物。MINOS 与外膜的两种前蛋白转运机制相互作用，即外膜转位酶 (TOM) 和分拣与装配机制 (SAM)。然而，MINOS 是否在外膜蛋白生物发生中发挥作用尚不清楚。我们已经剖析了 MINOS 与 TOM 和 SAM 的相互作用，并报告 MINOS 可以独立地与两种转位酶结合。MINOS 通过 Sam50 的保守多肽转运相关结构域与 SAM 复合物结合。缺乏 MINOS 的大亚基 mitofilin 的线粒体在其外膜 β-桶蛋白的生物发生中受损，而缺乏其他五个 MINOS 亚基之一的突变体线粒体以类似于野生型线粒体的方式导入β-桶蛋白。我们表明 mitofilin 在包括初始穿过 TOM 复合物的初始易位在内的 β-桶生物发生的早期阶段是必需的。我们得出的结论是，MINOS 与 TOM 和 SAM 独立相互作用，核心亚基 mitofilin 参与外膜 β-桶蛋白的生物发生。
