The mitochondrial intermembrane space: the most constricted mitochondrial sub-compartment with the largest variety of protein import pathways.
The mitochondrial intermembrane space: the most constricted mitochondrial sub-compartment with the largest variety of protein import pathways.
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线粒体膜间隙：最狭窄的线粒体亚区室，具有最多种类的蛋白质输入途径。
DOI：
10.1098/rsob.210002
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发表时间：
2021-03
期刊：
影响因子：
5.8
通讯作者：
Tokatlidis K
中科院分区：
文献类型：
--
作者：
Edwards R;Eaglesfield R;Tokatlidis K
线粒体膜间隙（IMS）是最狭窄的亚线粒体区室，容纳只有约5%的线粒体蛋白质组，但被赋予最大的可变性的蛋白质输入机制。在这篇综述中，我们总结了我们目前的知识，主要IMS进口途径的基础上氧化蛋白质折叠途径，并讨论了惊人的变化，其他IMS蛋白质进口途径。由于IMS定位的蛋白质只需要穿过线粒体外膜，它们不需要能量来源，如线粒体基质中的ATP水解或内膜电化学电位，这对于输入基质或插入内膜是至关重要的。我们还探索了几个非典型的IMS进口途径，仍然没有很好地理解，并指导定义不明确或完全未知的靶向肽。重要的是，许多IMS蛋白与几种人类疾病有关，因此了解它们如何到达IMS中的正常功能部位至关重要。在这篇综述的最后一部分，我们讨论了目前的理解，这样的IMS蛋白是如何支持一个大范围的人类疾病。
The mitochondrial intermembrane space (IMS) is the most constricted sub-mitochondrial compartment, housing only about 5% of the mitochondrial proteome, and yet is endowed with the largest variability of protein import mechanisms. In this review, we summarize our current knowledge of the major IMS import pathway based on the oxidative protein folding pathway and discuss the stunning variability of other IMS protein import pathways. As IMS-localized proteins only have to cross the outer mitochondrial membrane, they do not require energy sources like ATP hydrolysis in the mitochondrial matrix or the inner membrane electrochemical potential which are critical for import into the matrix or insertion into the inner membrane. We also explore several atypical IMS import pathways that are still not very well understood and are guided by poorly defined or completely unknown targeting peptides. Importantly, many of the IMS proteins are linked to several human diseases, and it is therefore crucial to understand how they reach their normal site of function in the IMS. In the final part of this review, we discuss current understanding of how such IMS protein underpin a large spectrum of human disorders.
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