Mitochondrial Biogenesis, Switching the Sorting Pathway of the Intermembrane Space Receptor Mia40
Mitochondrial Biogenesis, Switching the Sorting Pathway of the Intermembrane Space Receptor Mia40
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DOI：
10.1074/jbc.m805356200
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发表时间：
2008-10-31
影响因子：
4.8
通讯作者：
Pfanner, Nikolaus
中科院分区：
文献类型：
--
作者：
Chacinska, Agnieszka;Guiard, Bernard;Pfanner, Nikolaus
线粒体前体蛋白通过两种不同的途径进入膜间隙，前序列途径和氧化还原依赖的MIA途径。假设这些途径是独立的，并且转运不同的蛋白质。我们报告说，膜间隙受体Mia 40可以在这两种途径之间切换。在真菌中，Mia 40被合成为具有N-末端前序列的大蛋白，而在后生动物和植物中，Mia 40仅由保守的C-末端结构域组成。人MIA 40和酵母MIA 40的C-末端结构域（称为MIA 40（核心））独立于前序列的存在挽救了MIA 40缺陷型酵母的活力。通过MIA途径将纯化的Mia 40（核心）导入线粒体。随着细胞表达全长Mia 40和Mia 40（核心），我们证明，酵母Mia 40包含双重靶向信息，指导大的前体上的前序列途径和较小的Mia 40（核心）上的MIA途径，提出有趣的影响线粒体蛋白分选的演变。
Mitochondrial precursor proteins are directed into the intermembrane space via two different routes, the presequence pathway and the redox-dependent MIA pathway. The pathways were assumed to be independent and transport different proteins. We report that the intermembrane space receptor Mia40 can switch between both pathways. In fungi, Mia40 is synthesized as large protein with an N-terminal presequence, whereas in metazoans and plants, Mia40 consists only of the conserved C-terminal domain. Human MIA40 and the C-terminal domain of yeast Mia40 (termed Mia40(core)) rescued the viability of Mia40-deficient yeast independently of the presence of a presequence. Purified Mia40(core) was imported into mitochondria via the MIA pathway. With cells expressing both full-length Mia40 and Mia40(core), we demonstrate that yeast Mia40 contains dual targeting information, directing the large precursor onto the presequence pathway and the smaller Mia40(core) onto the MIA pathway, raising interesting implications for the evolution of mitochondrial protein sorting.