Molecular mechanisms of the control of yeast mitochondrial protein fluxes.

维持线粒体功能完整性的核心过程是将500-1000种不同的线粒体前体蛋白转运到线粒体。由于线粒体由四个区室组成，即外膜和内膜、膜间空间和基质，因此来自细胞质的线粒体蛋白的通量应该分为四个不同的亚通量，分别针对四个区室中的每个区室。在本研究中，我们旨在阐明酵母细胞线粒体蛋白通量的监测和控制机制。我们鉴定出线粒体蛋白易位子的5个新组分：Tom38、Tom13、Tim40、Tim15和Tim41。在我们努力为这些新成分分配线粒体蛋白进口的过程中，很明显，线粒体蛋白运输的途径比以前想象的要复杂得多，线粒体膜的易位和组装过程……通过线粒体易位复合物的合作，以一种高度复杂的方式得到更多的控制。此外，线粒体转运系统在线粒体蛋白通量的分支点上识别底物蛋白的目的地信号，并对其进行分类以纠正目的地路线是很重要的。在这方面，我们发现外膜的一般进口受体Tom20在提高靶向特异性和进口效率方面起着重要作用，内膜的Tim50起着前置受体的作用，而内膜中TIM22途径的底物蛋白具有TIM23途径的隐性靶向信号。一个重要但仍未解决的问题是，是什么驱动了线粒体的蛋白质通量。在这里，我们发现转运子的易位通道本身具有类似伴侣的活性，从而促进底物蛋白的展开，使其进入狭窄的转运子通道。少

The central process in the maintenance of functional integrity of mitochondria is the transport of 500-1000 different mitochondrial precursor proteins to mitochondria. Since mitochondria consist of four compartments, the outer and inner membranes, intermembrane space, and matrix, the flux of mitochondrial proteins from the cytosol should branch off in four different sub-fluxes that are directed for each of the four compartments. In the present study, we aimed at elucidation of the mechanisms for surveillance and control of the mitochondrial protein fluxes in yeast cells. We identified 5 new components, Tom38,Tom13,Tim40,Tim15,and Tim41,of the mitochondrial protein translocators. In the course of our efforts to assign roles in mitochondrial protein import to these new components, it has become evident that the pathways of mitochondrial protein transport are much more complex than previously envisaged and the processes of translocation across and assembly into mitochondrial membranes are … More controlled in a highly sophisticated manner by cooperation of the mitochondrial translocator complexes. Besides, it is important for the mitochondrial translocator systems to recognize destination signals of substrate proteins, at the branching points in the mitochondrial protein fluxes, and sort them to correct destination routes. In this connection, we found that the general import receptor, Tom20, in the outer membrane, plays important roles in increasing targeting specificity as well as import efficiency, that Tim50 in the inner membrane functions as a presequence receptor, and that substrate proteins for the TIM22 pathway in the inner membrane possess cryptic targeting signals for the TIM23 pathway. One of the important, but still unresolved questions is what drives the protein flux for mitochondria. Here we found that the translocation channel of the translocator itself has a chaperone-like activity, thereby promoting unfolding of the substrate proteins to be threaded into the narrow translocator channel. Less