Chen Opal S, Crisp Robert J, Valachovic Martin, Bard Martin, Winge Dennis R, Kaplan Jerry
Department of Pathology, School of Medicine, University of Utah, Salt Lake City, Utah 84132, USA.
J Biol Chem. 2004 Jul 9;279(28):29513-8. doi: 10.1074/jbc.M403209200. Epub 2004 Apr 28.
Saccharomyces cerevisiae responds to iron deprivation by increased transcription of the iron regulon, including the high affinity cell-surface transport system encoded by FET3 and FTR1. Here we demonstrate that transcription of these genes does not respond directly to cytosolic iron but rather to the mitochondrial utilization of iron for the synthesis of iron-sulfur (Fe-S) clusters. We took advantage of a mutant form of an iron-dependent enzyme in the sterol pathway (Erg25-2p) to assess cytosolic iron levels. We showed that disruption of mitochondrial Fe-S biosynthesis, which results in excessive mitochondrial iron accumulation, leads to transcription of the iron transport system independent of the cytosolic iron level. There is an inverse correlation between the activity of the mitochondrial Fe-S-containing enzyme aconitase and the induction of FET3. Regulation of transcription by Fe-S biosynthesis represents a mechanism by which cellular iron acquisition is integrated with mitochondrial iron metabolism.
酿酒酵母通过增加铁调节子的转录来响应铁缺乏，铁调节子包括由FET3和FTR1编码的高亲和力细胞表面转运系统。在这里，我们证明这些基因的转录并非直接响应胞质铁，而是响应线粒体利用铁来合成铁硫（Fe-S）簇。我们利用了固醇途径中一种铁依赖性酶的突变形式（Erg25-2p）来评估胞质铁水平。我们表明，线粒体Fe-S生物合成的破坏会导致线粒体铁过度积累，从而导致铁转运系统的转录，而与胞质铁水平无关。含线粒体Fe-S的酶乌头酸酶的活性与FET3的诱导之间存在负相关。Fe-S生物合成对转录的调节代表了一种机制，通过该机制细胞铁摄取与线粒体铁代谢得以整合。
