Molecular mechanisms of the control of yeast mitochondrial protein fluxes.

控制酵母线粒体蛋白质通量的分子机制。

基本信息

批准号：
15207009
负责人：
ENDO Toshiya
金额：
$ 32.2万
依托单位：
Nagoya University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (A)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2005
项目状态：
已结题

项目摘要

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

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。由于线粒体由四个隔室组成，因此外部和内部机制，膜间空间和基质，来自胞质醇的线粒体蛋白的通量应分支在四个针对四个隔室中的每个隔室的四个不同的子液管中分支。在本研究中，我们旨在阐明酵母细胞中线粒体蛋白通量监测和控制的机制。我们确定了线粒体蛋白转运剂的5个新组件，分别是Tom38，Tom13，Tim40，Tim15和Tim41。在我们为这些新组件中进口的线粒体蛋白中的作用而努力的过程中，已经证明了线粒体蛋白传输的途径比以前设想的要复杂得多，并且跨线粒体的易位过程和组合膜的易位过程……以高度控制的方式通过consotarial Complactrial complactrial complactrial complactrial complactrial Complactrial Complicatiral complactrial Complicatiral complactrial ComplaceRial complactrial complactrial complactrial。此外，在线粒体蛋白通量的分支点处，识别底物蛋白的目的地信号，并对其进行排序以纠正目的地路由，这一点很重要。在这方面，我们发现，外膜中的一般进口接收器TOM20在提高靶向特异性和进口效率方面起着重要作用，该内膜中的Tim50在内膜中起到了presequence接收器的作用，以及该内膜蛋白在TIM22途径中的底物蛋白在内部膜潜在的潜在膜潜在的Crypto Targets信号中的Tim22 path for Tim23 path。重要但尚未解决的问题之一是驱动线粒体蛋白质通量的原因。在这里，我们发现转运器本身的转运通道具有类似伴侣的活性，从而促进了底物蛋白的展开，该蛋白被拧到狭窄的转运器通道中。较少的