Coordinated Translocation of Presequence-Containing Precursor Proteins Across Two Mitochondrial Membranes: Knowns and Unknowns of How TOM and TIM23 Complexes Cooperate With Each Other.

Coordinated Translocation of Presequence-Containing Precursor Proteins Across Two Mitochondrial Membranes: Knowns and Unknowns of How TOM and TIM23 Complexes Cooperate With Each Other.
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DOI:
10.3389/fphys.2021.806426
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发表时间:
2021
影响因子:
4
通讯作者:
Mokranjac D
Mokranjac D
中科院分区:
医学2区
文献类型:
--
作者:
Genge MG;Mokranjac D

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绝大多数线粒体蛋白在核基因组中编码,并在细胞质核糖体上作为具有特定线粒体靶向信号的前体蛋白合成。然而,线粒体靶向信号非常多样化,大约70%的线粒体蛋白携带可切割的n端延伸,称为前序列。这些具有一个带正电和一个疏水表面的两亲螺旋分别借助外膜和内膜上的TOM和TIM23复合物将蛋白质靶向到线粒体基质上。蛋白质在两个线粒体膜上的易位不是彼此独立发生的。相反,在两种复合物相遇的膜间空间中,TOM和TIM23复合物的组分形成了一个复杂的蛋白质-蛋白质相互作用网络,该网络最初介导了前体序列的转移,然后介导了整个前体蛋白从线粒体外膜向内膜的转移。在这篇迷你综述中,我们总结了目前对TOM和TIM23复合物如何相互合作的理解,并强调了该领域未来的一些挑战和未解决的问题。
The vast majority of mitochondrial proteins are encoded in the nuclear genome and synthesized on cytosolic ribosomes as precursor proteins with specific mitochondrial targeting signals. Mitochondrial targeting signals are very diverse, however, about 70% of mitochondrial proteins carry cleavable, N-terminal extensions called presequences. These amphipathic helices with one positively charged and one hydrophobic surface target proteins to the mitochondrial matrix with the help of the TOM and TIM23 complexes in the outer and inner membranes, respectively. Translocation of proteins across the two mitochondrial membranes does not take place independently of each other. Rather, in the intermembrane space, where the two complexes meet, components of the TOM and TIM23 complexes form an intricate network of protein–protein interactions that mediates initially transfer of presequences and then of the entire precursor proteins from the outer to the inner mitochondrial membrane. In this Mini Review, we summarize our current understanding of how the TOM and TIM23 complexes cooperate with each other and highlight some of the future challenges and unresolved questions in the field.
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