Sirrenberg C, Endres M, Fölsch H, Stuart R A, Neupert W, Brunner M
Institut für Physiologische Chemie der Universität München, Germany.
Nature. 1998 Feb 26;391(6670):912-5. doi: 10.1038/36136.
Import of nuclear-encoded precursor proteins into mitochondria and their subsequent sorting into mitochondrial subcompartments is mediated by translocase enzymes in the mitochondrial outer and inner membranes. Precursor proteins carrying amino-terminal targeting signals are translocated into the matrix by the integral inner membrane proteins Tim23 and Tim17 in cooperation with Tim44 and mitochondrial Hsp70. We describe here the discovery of a new pathway for the transport of members of the mitochondrial carrier family and other inner membrane proteins that contain internal targeting signals. Two related proteins in the intermembrane space, Tim10/Mrs11 and Tim12/Mrs5, interact sequentially with these precursors and facilitate their translocation across the outer membrane, irrespective of the membrane potential. Tim10 and Tim12 are found in a complex with Tim22, which takes over the precursor and mediates its membrane-potential-dependent insertion into the inner membrane. This interaction of Tim10 and Tim12 with the precursors depends on the presence of divalent metal ions. Both proteins contain a zinc-finger-like motif with four cysteines and bind equimolar amounts of zinc ions.
核编码前体蛋白进入线粒体并随后分选到线粒体亚区室是由线粒体外膜和内膜中的转位酶介导的。携带氨基末端靶向信号的前体蛋白通过内膜整合蛋白Tim23和Tim17与Tim44及线粒体Hsp70协同作用转运到线粒体基质中。我们在此描述了线粒体载体家族成员和其他含有内部靶向信号的内膜蛋白运输新途径的发现。膜间隙中的两种相关蛋白Tim10/Mrs11和Tim12/Mrs5与这些前体蛋白依次相互作用，并促进它们穿过外膜的转运，而与膜电位无关。Tim10和Tim12与Tim22形成复合物，Tim22接管前体蛋白并介导其依赖膜电位插入内膜。Tim10和Tim12与前体蛋白的这种相互作用取决于二价金属离子的存在。这两种蛋白都含有一个具有四个半胱氨酸的锌指样基序，并结合等摩尔量的锌离子。
