A role for IOP1 in mammalian cytosolic iron-sulfur protein biogenesis
A role for IOP1 in mammalian cytosolic iron-sulfur protein biogenesis
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DOI：
10.1074/jbc.m708077200
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发表时间：
2008-04-04
影响因子：
4.8
通讯作者：
Lee, Frank S.
中科院分区：
文献类型：
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作者：
Song, Daisheng;Lee, Frank S.
哺乳动物细胞中胞质铁硫 (Fe-S) 蛋白的生物合成知之甚少。在酿酒酵母中，有一条专门用于胞质 Fe-S 蛋白成熟的途径，涉及多种必需蛋白。其中之一是 Nar1，有趣的是，它与纯铁氢化酶同源，这是一种古老的酶，可催化厌氧细菌中氢气的形成。哺乳动物细胞中有两个 Nar1 的直系同源物，即铁氢化酶样蛋白 1 (IOP1) 和 IOP2（也称为核前核纤层蛋白 A 识别因子）。我们检查了 IOP1 在哺乳动物细胞质 Fe-S 蛋白生物发生中的潜在作用。我们发现，HeLa 和 Hep3B 细胞中 IOP1 的敲低会降低胞质乌头酸酶（一种 Fe-S 蛋白）的活性，但不会降低线粒体乌头酸酶的活性。相比之下，IOP2 的敲低对两者都没有影响。 IOP1 敲除后乌头酸酶活性的降低可以通过 IOP1 的小干扰 RNA 抗性版本的表达来挽救。在失去 Fe-S 簇后，已知胞质乌头酸酶会转化为铁调节蛋白 1，与此一致，我们发现 IOP1 敲低会增加转铁蛋白受体 1 mRNA 水平并降低铁蛋白重链蛋白水平。 IOP1 敲除还会导致黄嘌呤氧化酶（一种独特的胞质 Fe-S 蛋白）活性降低。总而言之，这些结果提供了 IOP1 参与哺乳动物细胞质 Fe-S 蛋白成熟的证据。
The biogenesis of cytosolic iron-sulfur ( Fe-S) proteins in mammalian cells is poorly understood. In Saccharomyces cerevisiae, there is a pathway dedicated to cytosolic Fe-S protein maturation that involves several essential proteins. One of these is Nar1, which intriguingly is homologous to iron-only hydrogenases, ancient enzymes that catalyze the formation of hydrogen gas in anaerobic bacteria. There are two orthologues of Nar1 in mammalian cells, iron-only hydrogenase-like protein 1 ( IOP1) and IOP2 ( also known as nuclear prelamin A recognition factor). We examined IOP1 for a potential role in mammalian cytosolic Fe-Sproteinbiogenesis. We found that knockdown of IOP1 in both HeLa and Hep3B cells decreases the activity of cytosolic aconitase, an Fe-S protein, but not that of mitochondrial aconitase. Knockdown of IOP2, in contrast, had no effect on either. The decrease in aconitase activity upon IOP1 knockdown is rescued by expression of a small interference RNA-resistant version of IOP1. Upon loss of its Fe-S cluster, cytosolic aconitase is known to be converted to iron regulatory protein 1, and consistent with this, we found that IOP1 knockdown increases transferrin receptor 1 mRNA levels and decreases ferritin heavy chain protein levels. IOP1 knockdown also leads to a decrease in activity of xanthine oxidase, a distinct cytosolic Fe-S protein. Taken together, these results provide evidence that IOP1 is involved in mammalian cytosolic Fe-S protein maturation.