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Molecular mechanisms and regulation of the import of hydrophobic transport proteins from the cytosol into the mitochondrial inner membrane

疏水转运蛋白从细胞质输入线粒体内膜的分子机制和调控

基本信息

批准号：
244743982
负责人：
Professor Dr. Nikolaus Pfanner
金额：
--
依托单位：
Institut für Biochemie und Molekularbiologie
依托单位国家：
德国
项目类别：
Research Grants
财政年份：
2013
资助国家：
德国
起止时间：
2012-12-31 至 2017-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/244743982?language=en
关键词：
Molecular mechanisms regulation import hydrophobic

项目摘要

Mitochondria are essential cell organelles. They are of central importance for energy conversion and the metabolism of cells. Defects of mitochondria lead to severe diseases, in particular of the nervous system. The mitochondrial inner membrane contains a large number of hydrophobic transport proteins, which are crucial for the translocation of metabolites between mitochondria and the rest of the cell. The transport proteins are synthesized as precursors in the cytosol and are imported in a multistep process that involves translocases of mitochondrial outer and inner membranes and molecular chaperones in cytosol and intermembrane space. However, major questions of the mechanisms and regulation of the translocases of both mitochondrial membranes have not been addressed. We have established an experimental system to study the transport of hydrophobic precursor proteins and their interaction with import components by a combination of genetic, biochemical, molecular biological and cell biological approaches. This project pursues three main aims. (i) Characterization of the reaction cycle of precursor proteins, cytosolic chaperones and receptors of the mitochondrial outer membrane, as well as their regulation. (ii) Analysis of the molecular environment of hydrophobic precursor proteins during transport across the outer membrane and insertion into the inner membrane. The mechanism of recognition of precursor proteins at the inner membrane and the regulation of transport will be studied. (iii) Analysis of the assembly of the inner membrane translocase and function of new partner proteins. With these studies, we aim to characterize fundamental mechanisms of the import of hydrophobic transport proteins from the cytosol in the mitochondrial inner membrane, a process that is essential for cell viability.

线粒体是细胞的重要细胞器。它们对能量转换和细胞新陈代谢至关重要。线粒体缺陷会导致严重的疾病，特别是神经系统的疾病。线粒体内膜含有大量的疏水转运蛋白，对线粒体和细胞其他部分之间的代谢产物的转运至关重要。转运蛋白作为前体在胞浆中合成，并通过一个多步骤的过程输入，其中包括线粒体外膜和内膜的转位以及胞浆和膜间隙中的分子伴侣。然而，关于这两种线粒体膜转位酶的机制和调控的主要问题还没有得到解决。我们建立了一个实验系统，结合遗传学、生物化学、分子生物学和细胞生物学的方法研究疏水前体蛋白的运输及其与进口成分的相互作用。这个项目追求三个主要目标。(1)前体蛋白、胞质伴侣和线粒体外膜受体的反应周期特征及其调节。(2)分析疏水前体蛋白在跨外膜运输和插入内膜过程中的分子环境。将研究前体蛋白在内膜上的识别机制和转运的调节。(Iii)分析内膜转位酶的组装和新的配对蛋白的功能。通过这些研究，我们的目标是表征从线粒体内膜的胞浆中输入疏水运输蛋白的基本机制，这是一个对细胞生存至关重要的过程。