An essential function of the mitochondrial sulfhydryl oxidase Erv1p/ALR in the maturation of cytosolic Fe/S proteins
An essential function of the mitochondrial sulfhydryl oxidase Erv1p/ALR in the maturation of cytosolic Fe/S proteins
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DOI：
10.1093/embo-reports/kve161
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发表时间：
2001-08-01
期刊：
影响因子：
7.7
通讯作者：
Lill, R
中科院分区：
文献类型：
--
作者：
Lange, H;Lisowsky, T;Lill, R
Fe/S团簇的生物发生涉及许多必需的线粒体蛋白。在这里，我们确定了必要的Erv 1 p的酿酒酵母线粒体作为一种新的组件，是专门需要的Fe/S蛋白质在胞质溶胶中的成熟，但不是在线粒体。此外，Erv 1 p被发现是重要的细胞铁稳态。同源的哺乳动物蛋白ALR（“肝再生增强因子”），也称为肝细胞生成素，可以在功能上取代Erv 1 p的缺陷，因此代表了酵母Erv 1 p的哺乳动物直向同源物。以前，据报道ALR的片段表现出作为细胞外肝营养生长因子的活性。Erv 1 p和全长ALR都位于线粒体膜间隙中，是该隔室的第一个组成部分，在细胞溶质Fe/S蛋白的生物合成中发挥作用。Erv 1 p/ALR很可能在线粒体ABC转运蛋白Atm 1 p/ABC 7/Sta 1的下游发挥作用，后者也在这一重要的生化过程中执行特定的任务。
Biogenesis of Fe/S clusters involves a number of essential mitochondrial proteins. Here, we identify the essential Erv1p of Saccharomyces cerevisia mitochondria as a novel component that is specifically required for the maturation of Fe/S proteins in the cytosol, but not in mitochondria. Furthermore, Erv1p was found to be important for cellular iron homeostasis. The homologous mammalian protein ALR ('augmenter of liver regeneration'), also termed hepatopoietin, can functionally replace defects in Erv1p and thus represents the mammalian orthologue of yeast Erv1p. Previously, a fragment of ALR was reported to exhibit an activity as an extracellular hepatotrophic growth factor. Both Erv1p and full-length ALR are located in the mitochondrial intermembrane space and represent the first components of this compartment with a role in the biogenesis of cytosolic Fe/S proteins. It is likely that Erv1p/ALR operates downstream of the mitochondrial ABC transporter Atm1p/ABC7/Sta1, which also executes a specific task in this essential biochemical process.