Iron-induced oligomerization of yeast frataxin homologue Yfh1 is dispensable in vivo
Iron-induced oligomerization of yeast frataxin homologue Yfh1 is dispensable in vivo
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DOI：
10.1038/sj.embor.7400272
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发表时间：
2004-11-01
期刊：
影响因子：
7.7
通讯作者：
Craig, EA
中科院分区：
文献类型：
--
作者：
Aloria, K;Schilke, B;Craig, EA
神经退行性疾病弗里德赖希共济失调是由线粒体基质蛋白 frataxin 水平降低引起的。 frataxin 的体内作用尚有争议。 Frataxin 及其酵母同源物 Yfh1 以寡聚物形式结合多个铁原子，并被认为是一种重要的铁储存蛋白。我们发现了一个在铁诱导的寡聚化中存在缺陷的突变体 Yfh1。这种突变蛋白能够在功能上取代野生型 Yfh1，即使在低水平表达、线粒体铁水平较高以及在具有 YFH1 缺失的合成生长缺陷基因缺失的突变菌株中也是如此。寡聚化缺陷的 Yfh1 在体内发挥作用的能力表明，寡聚化以及寡聚化诱导的铁储存并不是 Yfh1 的关键功能。相反，这种寡聚化缺陷突变体与 Isu 蛋白相互作用的能力表明 Yfh1 在铁硫簇生物合成中具有更直接的作用。
The neurodegenerative disease Friedreich's ataxia is caused by reduced levels of frataxin, a mitochondrial matrix protein. The in vivo role of frataxin is under debate. Frataxin, as well as its yeast homologue Yfh1, binds multiple iron atoms as an oligomer and has been proposed to function as a crucial iron-storage protein. We identified a mutant Yfh1 defective in iron-induced oligomerization. This mutant protein was able to replace functionally wild-type Yfh1, even when expressed at low levels, when mitochondrial iron levels were high and in mutant strains having deletions of genes that had synthetic growth defects with a YFH1 deletion. The ability of an oligomerization-deficient Yfh1 to function in vivo suggests that oligomerization, and thus oligomerization-induced iron storage, is not a critical function of Yfh1. Rather, the capacity of this oligomerization-deficient mutant to interact with the Isu protein suggests a more direct role of Yfh1 in iron-sulphur cluster biogenesis.