Institut für Biochemie und Molekularbiologie, ZBMZ, Universität Freiburg, 79104 Freiburg, Germany.
Institut für Biochemie und Molekularbiologie, ZBMZ, Universität Freiburg, 79104 Freiburg, Germany; Fakultät für Biologie, Universität Freiburg, 79104 Freiburg, Germany.
Mol Cell. 2014 Dec 4;56(5):641-52. doi: 10.1016/j.molcel.2014.10.010. Epub 2014 Nov 13.
The majority of preproteins destined for mitochondria carry N-terminal presequences. The presequence translocase of the inner mitochondrial membrane (TIM23 complex) plays a central role in protein sorting. Preproteins are either translocated through the TIM23 complex into the matrix or are laterally released into the inner membrane. We report that the small hydrophobic protein Mgr2 controls the lateral release of preproteins. Mgr2 interacts with preproteins in transit through the TIM23 complex. Overexpression of Mgr2 delays preprotein release, whereas a lack of Mgr2 promotes preprotein sorting into the inner membrane. Preproteins with a defective inner membrane sorting signal are translocated into the matrix in wild-type mitochondria but are released into the inner membrane in Mgr2-deficient mitochondria. We conclude that Mgr2 functions as a lateral gatekeeper of the mitochondrial presequence translocase, providing quality control for the membrane sorting of preproteins.
大多数定位于线粒体的前体蛋白携带 N 端前导序列。线粒体内膜的前体蛋白转位酶（TIM23 复合物）在蛋白质分拣中起着核心作用。前体蛋白要么通过 TIM23 复合物穿过进入基质，要么横向释放到内膜中。我们报告说，小疏水性蛋白Mgr2 控制前体蛋白的横向释放。Mgr2 与通过 TIM23 复合物转运的前体蛋白相互作用。Mgr2 的过表达会延迟前体蛋白的释放，而 Mgr2 的缺乏则会促进前体蛋白分拣到内膜中。具有缺陷的内膜分拣信号的前体蛋白在野生型线粒体中被转运到基质中，但在 Mgr2 缺陷型线粒体中被释放到内膜中。我们得出结论，Mgr2 作为线粒体前导序列转位酶的横向门控蛋白发挥作用，为前体蛋白的膜分拣提供质量控制。
