Divergence of Erv1-Associated Mitochondrial Import and Export Pathways in Trypanosomes and Anaerobic Protists
Divergence of Erv1-Associated Mitochondrial Import and Export Pathways in Trypanosomes and Anaerobic Protists
复制标题
DOI：
10.1128/ec.00304-12
复制
发表时间：
2013-02-01
期刊：
影响因子：
--
通讯作者：
Allen, James W. A.
中科院分区：
文献类型：
--
作者：
Basu, Somsuvro;Leonard, Joanne C.;Allen, James W. A.
在酵母（酿酒酵母）和动物中，巯基氧化酶Erv 1与Mia 40一起在线粒体膜间隙（IMS）中的许多富含半胱氨酸的蛋白质的输入和氧化折叠中发挥作用。Erv 1也是细胞质中Fe-S簇组装所必需的，其使用至少一种衍生的前体。在这里，我们的特点是一个必不可少的Erv 1直向同源物从原生生物布氏锥虫（TbERV 1），自然缺乏Mia 40同源物。我们报告了生理相关氧化剂细胞色素c和O-2的动力学参数，意外地发现O-2和细胞色素c同时被还原，并证明TbERV 1对O-2的有效还原不依赖于由保守的组氨酸和酪氨酸残基定义的简单O-2通道。TbERV 1 RNA干扰（RNAi）后的大规模线粒体肿胀提供了证据，表明锥虫Erv 1在IMS蛋白输入中发挥作用，尽管酵母和动物输入途径中天然缺乏关键参与者Mia 40。这表明线粒体细胞生物学中最近建立的范式存在显著的进化差异。基因的系统基因组分析也指出了TbERV 1在胞质Fe-S簇组装中的保守作用。相反，内阿米巴、毛滴虫和贾第鞭毛虫中涉及胞质Fe-S组装的前体递送的基因的丢失表明厌氧与好氧真核生物中活化的铁或硫物质的细胞内运输途径的根本差异。
In yeast (Saccharomyces cerevisiae) and animals, the sulfhydryl oxidase Erv1 functions with Mia40 in the import and oxidative folding of numerous cysteine-rich proteins in the mitochondrial intermembrane space (IMS). Erv1 is also required for Fe-S cluster assembly in the cytosol, which uses at least one mitochondrially derived precursor. Here, we characterize an essential Erv1 orthologue from the protist Trypanosoma brucei (TbERV1), which naturally lacks a Mia40 homolog. We report kinetic parameters for physiologically relevant oxidants cytochrome c and O-2, unexpectedly find O-2 and cytochrome c are reduced simultaneously, and demonstrate that efficient reduction of O-2 by TbERV1 is not dependent upon a simple O-2 channel defined by conserved histidine and tyrosine residues. Massive mitochondrial swelling following TbERV1 RNA interference (RNAi) provides evidence that trypanosome Erv1 functions in IMS protein import despite the natural absence of the key player in the yeast and animal import pathways, Mia40. This suggests significant evolutionary divergence from a recently established paradigm in mitochondrial cell biology. Phylogenomic profiling of genes also points to a conserved role for TbERV1 in cytosolic Fe-S cluster assembly. Conversely, loss of genes implicated in precursor delivery for cytosolic Fe-S assembly in Entamoeba, Trichomonas, and Giardia suggests fundamental differences in intracellular trafficking pathways for activated iron or sulfur species in anaerobic versus aerobic eukaryotes.