The yeast scaffold proteins Isu1p and Isu2p are required inside mitochondria for maturation of cytosolic Fe/S proteins
The yeast scaffold proteins Isu1p and Isu2p are required inside mitochondria for maturation of cytosolic Fe/S proteins
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DOI：
10.1128/mcb.24.11.4848-4857.2004
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发表时间：
2004-06-01
影响因子：
5.3
通讯作者：
Lill, R
中科院分区：
文献类型：
--
作者：
Gerber, J;Neumann, K;Lill, R
铁硫蛋白（Fe/S）位于线粒体、细胞质和细胞核中。线粒体Fe/S蛋白通过铁硫簇（ISC）组装机制成熟。关于Fe/S蛋白在细胞质和细胞核中的形成知之甚少。已经注意到线粒体在胞质Fe/S蛋白成熟中的功能，但是在线粒体外已经检测到少量的一些ISC组分。在这里，我们研究了高度保守的酵母蛋白Isu 1 p和Isu 2 p，这为Fe/S簇合成提供了一个支架。我们问是否需要的Isu蛋白质的生物合成的胞质Fe/S簇和在亚细胞隔室的Isu蛋白质是必需的。Isu蛋白被认为是必不可少的从头生物合成的线粒体和胞质Fe/S蛋白。一些证据表明，Isu 1 p和Isu 2 p必须位于线粒体内，以执行其功能，在胞质Fe/S蛋白成熟。我们无法错误定位Isu 1 p的胞质溶胶由于存在多个，独立的线粒体靶向信号在这种蛋白质。此外，细菌同源物IscU和人Isu蛋白（部分）补充了酵母Isu蛋白耗尽细胞在生长速率、Fe/S蛋白生物合成和铁稳态方面的缺陷，但仅在靶向线粒体之后。总之，我们的数据表明，Isu蛋白需要定位在线粒体中，以满足其功能要求的Fe/S蛋白在胞质中的成熟。
Iron-sulfur (Fe/S) proteins are located in mitochondria, cytosol, and nucleus. Mitochondrial Fe/S proteins are matured by the iron-sulfur cluster (ISC) assembly machinery. Little is known about the formation of Fe/S proteins in the cytosol and nucleus. A function of mitochondria in cytosolic Fe/S protein maturation has been noted, but small amounts of some ISC components have been detected outside mitochondria. Here, we studied the highly conserved yeast proteins Isu1p and Isu2p, which provide a scaffold for Fe/S cluster synthesis. We asked whether the Isu proteins are needed for biosynthesis of cytosolic Fe/S clusters and in which subcellular compartment the Isu proteins are required. The Isu proteins were found to be essential for de novo biosynthesis of both mitochondrial and cytosolic Fe/S proteins. Several lines of evidence indicate that Isu1p and Isu2p have to be located inside mitochondria in order to perform their function in cytosolic Fe/S protein maturation. We were unable to mislocalize Isu1p to the cytosol due to the presence of multiple, independent mitochondrial targeting signals in this protein. Further, the bacterial homologue IscU and the human Isu proteins (partially) complemented the defects of yeast Isu protein-depleted cells in growth rate, Fe/S protein biogenesis, and iron homeostasis, yet only after targeting to mitochondria. Together, our data suggest that the Isu proteins need to be localized in mitochondria to fulfill their functional requirement in Fe/S protein maturation in the cytosol.