Oxidative stress inhibits the mitochondrial import of preproteins and leads to their degradation
Oxidative stress inhibits the mitochondrial import of preproteins and leads to their degradation
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DOI：
10.1006/excr.2000.5096
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发表时间：
2001-02-01
影响因子：
3.7
通讯作者：
Mori, M
中科院分区：
文献类型：
--
作者：
Wright, G;Terada, K;Mori, M
对于构成其结构元件和代谢途径的大多数蛋白质而言，蛋白质依赖于胞质合成的前蛋白的输入。本文研究了氧化还原条件对哺乳动物线粒体前蛋白输入和加工的影响。在完整的细胞中，氧化条件导致成熟OTC水平降低及其前蛋白的积累。暗示线粒体输入损伤，荧光的pOTC-GFP（蛋白质，其中pOTC的前序列融合到绿色荧光蛋白）转染细胞减少百草枯治疗，而胞质野生型GFP基本上保持不受影响。蛋白酶体抑制剂可促进前蛋白的积累。我们观察到，由于氧化条件或本质上较慢的输入速率，未能输入的前体蛋白容易降解。还发现蛋白酶体的抑制导致更高水平的移位酶外膜蛋白20（Tom 20）和线粒体的核周积累。这些研究表明，细胞氧化还原条件影响线粒体输入，这反过来又影响线粒体蛋白水平。蛋白酶体在这一过程中的作用，并在一般线粒体功能也表明。(C)北京：科学出版社.
The mitochondrion depends upon the import of cytosolically synthesized preproteins for most of the proteins that comprise its structural elements and metabolic pathways. Here we have examined the influence of redox conditions on mitochondrial preprotein import and processing by mammalian mitochondria, Paraquat pretreatment of isolated mitochondria inhibited the subsequent import preornithine transcarbamylase (pOTC) in vitro. In intact cells oxidizing conditions led to decreased levels of mature OTC and accumulation of its preprotein. Implicating a mitochondrial import lesion, the fluorescence of pOTC-GFP (a protein in which the presequence of pOTC was fused to green fluorescent protein) transfected cells was decreased by paraquat treatment while cytosolic wild-type GFP remained largely unaffected. The accumulation of preproteins was enhanced by proteasome inhibitors. We observed that precursor proteins that failed to be imported, due to oxidizing conditions or an intrinsically slower import rate, are susceptible to degradation. Inhibition of the proteasome was also found to lead to higher levels of the translocase outer membrane protein 20 (Tom20) and to the perinuclear accumulation of mitochondria, These studies indicate that cellular redox conditions influence mitochondrial import, which, in turn, affects mitochondrial protein levels. A role for the proteasome in this process and in general mitochondrial function was also indicated. (C) 2001 Academic Press.