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、膜间隙和基质，因此来自胞质溶胶的线粒体蛋白质的通量应该分支为四个不同的子通量，分别针对四个区室中的每一个。在本研究中，我们的目的是阐明机制的监督和控制的线粒体蛋白质通量在酵母细胞。我们鉴定了5个新的线粒体蛋白质转运子元件，即Tom 38、Tom 13、Tim 40、Tim 15和Tim 41。在我们努力将线粒体蛋白质输入中的作用分配给这些新组分的过程中，已经变得明显的是，线粒体蛋白质转运的途径比以前设想的要复杂得多，并且跨线粒体膜的易位和组装到线粒体膜中的过程是复杂的。 ...更多信息 通过线粒体易位复合物的合作以高度复杂的方式控制。此外，重要的是线粒体转运系统识别底物蛋白的目的地信号，在线粒体蛋白流的分支点，并将它们分类到正确的目的地路线。在这方面，我们发现外膜中的一般输入受体Tom 20在增加靶向特异性以及输入效率方面起重要作用，内膜中的Tim 50作为前序列受体起作用，内膜中的TIM 22途径的底物蛋白具有TIM 23途径的隐蔽靶向信号。其中一个重要但尚未解决的问题是，是什么驱动了线粒体的蛋白质流动。在这里，我们发现，易位本身的易位通道具有分子伴侣样活性，从而促进底物蛋白的解折叠，以进入狭窄的易位通道。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