Translational regulation of mammalian and Drosophila citric acid cycle enzymes via iron-responsive elements
Translational regulation of mammalian and Drosophila citric acid cycle enzymes via iron-responsive elements
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DOI：
10.1073/pnas.93.10.4925
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发表时间：
1996-05-14
影响因子：
11.1
通讯作者：
Hentze, MW
中科院分区：
文献类型：
--
作者：
Gray, NK;Pantopoulos, K;Hentze, MW
铁响应元件（IREs）和铁调节蛋白（IRP）对铁的吸收、储存和利用的转录后调控为许多动物体内铁稳态的调节提供了分子框架。我们已经确定了两种不同的线粒体柠檬酸循环酶的mRNA中的IREs的特征。黑腹果蝇IRP与编码琥珀酸脱氢酶（SDH）铁硫蛋白（Ip）亚基的mRNA的5'非翻译区中的IRE结合。这种相互作用在果蝇胚胎发育过程中受到发育调控。在无细胞翻译系统中，重组IRP-1对带有Son IRE的报告mRNA施加高度特异性的翻译抑制，而SDH-Ip mRNA的翻译在D.黑腹施耐德细胞。在哺乳动物中，在来自两个物种的线粒体顺乌头酸酶mRNA的5'非翻译区中鉴定出IRE。重组IRP-1以与铁蛋白IRE控制的翻译类似的效率抑制顺乌头酸酶合成。哺乳动物IRP和乌头酸酶IRE之间的相互作用受到铁、一氧化氮和氧化应激（H2 O2）的调节，表明这三种信号可以控制线粒体乌头酸酶mRNA的表达。我们的研究结果确定了脊椎动物和无脊椎动物的能量和铁代谢之间的调节联系，并建议IRE/IRP调节系统的生物功能，除了维持铁稳态。
The posttranscriptional control of iron uptake, storage, and utilization by iron-responsive elements (IREs) and iron regulatory proteins (IRPs) provides a molecular framework for the regulation of iron homeostasis in many animals. We have identified and characterized IREs in the mRNAs for two different mitochondrial citric acid cycle enzymes. Drosophila melanogaster IRP binds to an IRE in the 5' untranslated region of the mRNA encoding the iron-sulfur protein (Ip) subunit of succinate dehydrogenase (SDH). This interaction is developmentally regulated during Drosophila embryogenesis. In a cell-free translation system, recombinant IRP-1 imposes highly specific translational repression on a reporter mRNA bearing the Son IRE, and the translation of SDH-Ip mRNA is iron regulated in D. melanogaster Schneider cells. In mammals, an IRE was identified in the 5' untranslated regions of mitochondrial aconitase mRNAs from two species, Recombinant IRP-1 represses aconitase synthesis with similar efficiency as ferritin IRE-controlled translation. The interaction between mammalian IRPs and the aconitase IRE is regulated by iron, nitric oxide, and oxidative stress (H2O2), indicating that these three signals can control the expression of mitochondrial aconitase mRNA. Our results identify a regulatory link between energy and iron metabolism in vertebrates and invertebrates, and suggest biological functions for the IRE/IRP regulatory system in addition to the maintenance of iron homeostasis.