ISCA1 is essential for mitochondrial Fe(4)S(4) biogenesis in vivo.
ISCA1 is essential for mitochondrial Fe(4)S(4) biogenesis in vivo.
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DOI：
10.1038/ncomms15124
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发表时间：
2017-05-11
影响因子：
16.6
通讯作者：
Martelli A
中科院分区：
文献类型：
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作者：
Beilschmidt LK;Ollagnier de Choudens S;Fournier M;Sanakis I;Hograindleur MA;Clémancey M;Blondin G;Schmucker S;Eisenmann A;Weiss A;Koebel P;Messaddeq N;Puccio H;Martelli A
哺乳动物A型蛋白ISCA1和ISCA2是铁-硫簇(Fe-S)生物发生过程中进化保守的蛋白质。最近的研究表明，ISCA1和ISCA2形成异源复合体，参与线粒体Fe4S4蛋白的成熟。在这里，我们报道了小鼠ISCA1和ISCA2是含有Fe2S2的蛋白，它结合了铁-S载体蛋白的所有特征。我们使用生化、光谱和体内的方法来证明，尽管形成了一个复合体，但ISCA1和ISCA2与已故的铁-S机械的组件建立了离散的相互作用。令人惊讶的是，在小鼠骨骼肌和神经元原代培养中的击倒实验表明，线粒体Fe4S4蛋白的生物发生需要ISCA1，而不是ISCA2。总之，我们的数据表明，似乎存在对ISCA1、ISCA2和ISCA1-ISCA2复合体有不同要求的细胞过程。线粒体蛋白ISCA1和ISCA2形成一个复合体，参与铁-S团簇的生物发生。本文报道了IscA_1和IscA_2与铁-S机制中蛋白质的相互作用不同，在一定条件下，IscA_2似乎是铁-S生物发生所必需的。
Mammalian A-type proteins, ISCA1 and ISCA2, are evolutionarily conserved proteins involved in iron–sulfur cluster (Fe–S) biogenesis. Recently, it was shown that ISCA1 and ISCA2 form a heterocomplex that is implicated in the maturation of mitochondrial Fe4S4 proteins. Here we report that mouse ISCA1 and ISCA2 are Fe2S2-containing proteins that combine all features of Fe–S carrier proteins. We use biochemical, spectroscopic and in vivo approaches to demonstrate that despite forming a complex, ISCA1 and ISCA2 establish discrete interactions with components of the late Fe–S machinery. Surprisingly, knockdown experiments in mouse skeletal muscle and in primary cultures of neurons suggest that ISCA1, but not ISCA2, is required for mitochondrial Fe4S4 proteins biogenesis. Collectively, our data suggest that cellular processes with different requirements for ISCA1, ISCA2 and ISCA1–ISCA2 complex seem to exist. The mitochondrial proteins ISCA1 and ISCA2 form a complex that is involved in the biogenesis of Fe–S clusters. Here the authors report that ISCA1 and ISCA2 interact differently with proteins of the Fe–S machinery and that under certain conditions, ISCA2 seems dispensable for Fe–S biogenesis.