Identification of FRA1 and FRA2 as genes involved in regulating the yeast iron regulon in response to decreased mitochondrial iron-sulfur cluster synthesis
Identification of FRA1 and FRA2 as genes involved in regulating the yeast iron regulon in response to decreased mitochondrial iron-sulfur cluster synthesis
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DOI：
10.1074/jbc.m801160200
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发表时间：
2008-04-18
影响因子：
4.8
通讯作者：
Kaplan, Jerry
中科院分区：
文献类型：
--
作者：
Kumanovics, Attila;Chen, Opal S.;Kaplan, Jerry
酿酒酵母中线粒体 Fe-S 簇合成与铁敏感转录因子 Aft1 在调节铁转运系统表达方面之间的联系性质尚不清楚。通过基因筛选，我们鉴定了两种新型胞质蛋白 Fra1 和 Fra2，它们是解释线粒体 Fe-S 合成信号的复合物的一部分。我们发现 FRA1 (YLL029W) 和 FRA2 (YGL220W) 的突变导致铁调节子的转录增加。在高铁培养基中培养的细胞中，任一 FRA 基因的缺失都会导致低铁敏感转录因子 Aft1 易位到细胞核中，并在细胞核中占据 FET3 启动子。任一 FRA 基因的删除与删除这两个基因对转录具有相同的影响，并且不会因线粒体 Fe-S 簇合成的损失而激活铁调节子。这些观察结果表明 FRA 蛋白与 Fe-S 簇合成处于相同的信号转导途径。我们证明 Fra1 和 Fra2 在细胞质中以不依赖铁的方式相互作用。 Fra1-Fra2 复合物以不依赖于铁的方式与两种胞质单硫醇谷氧还蛋白 Grx3 和 Grx4 结合。这些结果表明 Fra-Grx 复合物是线粒体 Fe-S 簇的产生和铁调节子转录之间的中间体。
The nature of the connection between mitochondrial Fe-S cluster synthesis and the iron-sensitive transcription factor Aft1 in regulating the expression of the iron transport system in Saccharomyces cerevisiae is not known. Using a genetic screen, we identified two novel cytosolic proteins, Fra1 and Fra2, that are part of a complex that interprets the signal derived from mitochondrial Fe-S synthesis. We found that mutations in FRA1 (YLL029W) and FRA2 (YGL220W) led to an increase in transcription of the iron regulon. In cells incubated in high iron medium, deletion of either FRA gene results in the translocation of the low iron-sensing transcription factor Aft1 into the nucleus, where it occupies the FET3 promoter. Deletion of either FRA gene has the same effect on transcription as deletion of both genes and is not additive with activation of the iron regulon due to loss of mitochondrial Fe-S cluster synthesis. These observations suggest that the FRA proteins are in the same signal transduction pathway as Fe-S cluster synthesis. We show that Fra1 and Fra2 interact in the cytosol in an iron-independent fashion. The Fra1-Fra2 complex binds to Grx3 and Grx4, two cytosolic monothiol glutaredoxins, in an iron-independent fashion. These results show that the Fra-Grx complex is an intermediate between the production of mitochondrial Fe-S clusters and transcription of the iron regulon.