Molecular mechanisms of the control of yeast mitochondrial protein fluxes.

维持线粒体功能完整性的中心过程是将500-1000种不同的线粒体前体蛋白运输到线粒体。由于线粒体由四个隔室组成，即外膜和内膜、膜间隙和基质，因此来自细胞质的线粒体蛋白质的通量应该分成四个不同的子通量，分别指向这四个隔室中的每一个。在本研究中，我们旨在阐明酵母细胞中线粒体蛋白通量的监测和控制机制。我们鉴定了线粒体蛋白转运体的5个新组分，Tom38、Tom13、Tim40、Tim15和Tim41。在我们努力将线粒体蛋白质输入中的角色分配给这些新组件的过程中，很明显，线粒体蛋白质运输的途径比之前想象的要复杂得多，跨线粒体膜转位和组装到线粒体膜的过程是…通过线粒体转位复合体的合作，以高度复杂的方式进行更多的控制。此外，对于线粒体转位系统来说，重要的是识别底物蛋白在线粒体蛋白通量中的分支点的目的地信号，并将它们分类以正确的目的地路线。在这方面，我们发现外膜的通用导入受体Tom20在提高靶向特异性和导入效率方面发挥着重要作用，内膜的Tim50起着前序列受体的作用，内膜TIM22途径的底物蛋白对TIM23途径具有隐蔽的靶向信号。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流动。在这里，我们发现转位蛋白本身的转位通道具有伴侣样活性，从而促进底物蛋白的展开，使其进入狭窄的转位通道。较少

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