线粒体铁 - 硫簇生物合成
中文名称
通路描述
线粒体铁 - 硫簇生物合成涉及线粒体基质中铁 - 硫簇 (ISC) 组装机器。铁离子通过线粒体内膜上的铁蛋白 -1 (SLC25A37) 和铁蛋白 -2 (SLC25A28) 被转运至线粒体基质。铁蛋白 -1 在红细胞中富集，而铁蛋白 -2 是普遍存在的。铁蛋白 -1 在铁蛋白 -1 与 ISD11 形成的复合物中结合亚铁离子。Cys 脱硫酸酶 NFS1 与 ISD11 形成复合物，将亚铁离子转化为硫酸亚铁，形成过硫酸盐，用于在 ISCU 上形成簇。NFS1 与 ISD11 之间的相互作用对于脱硫酸酶活性是必需的。铁蛋白 -1 与含有 NFS1、ISD11 和 ISCU 的复合物结合，并作为铁供体供 ISCU 使用，或作为别构开关激活硫转移和 Fe-S 簇组装 (Tsai and Barondeau 2010)。簇的形成还涉及铁蛋白还原酶和铁蛋白。ISCU 最初形成含有 2 个铁原子和 2 个硫原子的 [2Fe-2S] 簇。它们通过 HSP70-HSC20 伴侣蛋白和单硫谷胱甘肽 GLRX5 的功能释放，用于 [2Fe-2S] 蛋白的组装。更大簇如 [4Fe-4S] 簇的形成可能涉及 ISCA1、ISCA2 和 IBA57 的功能。簇通过专门的靶向因子如 IND1、NFU1 和 BOLA3 转移给无 apo 酶如呼吸复合物、脱氢酶和丙二酸合酶。
英文描述
Mitochondrial iron-sulfur cluster biogenesis Iron-sulfur (Fe-S) proteins are localized in the cytosol, nucleus, and mitochondria of mammalian cells (reviewed in Stemmler et al. 2010, Rouault 2012, Bandyopadhyay et al. 2008, Lill 2009, Lill et al. 2012). Fe-S protein biogenesis in the mitochondrial matrix involves the iron-sulfur cluster (ISC) assembly machinery. Ferrous iron is transported across the inner mitochondrial membrane into the mitochondrial matrix by Mitoferrin-1 (SLC25A37) and Mitoferrin-2 (SLC25A28). (Mitoferrin-1 is enriched in erythroid cells while Mitoferrin-2 is ubiquitous.) Frataxin binds ferrous iron in the mitochondrial matrix. The cysteine desulfurase NFS1 in a subcomplex with ISD11 provides the sulfur by converting cyteine into alanine and forming a persulfide which is used for cluster formation on ISCU, the scaffold protein. Interaction between NFS1 and ISD11 is necessary for desulfurase activity. Frataxin binds to a complex containing NFS1, ISD11, and ISCU and is proposed to function as an iron donor to ISCU or as an allosteric switch that activates sulfur transfer and Fe-S cluster assembly (Tsai and Barondeau 2010). Cluster formation also involves the electron transfer chain ferredoxin reductase and ferredoxin. ISCU initially forms clusters containing 2 iron atoms and 2 sulfur atoms ([2Fe-2S] clusters). They are released by the function of HSP70-HSC20 chaperones and the monothiol glutaredoxin GLRX5 and used for assembly of [2Fe-2S] proteins. Assembly of larger clusters such as [4Fe-4S] clusters may involve the function of ISCA1, ISCA2, and IBA57. The clusters are transferred to apo-enzymes such as the respiratory complexes, aconitase, and lipoate synthase through dedicated targeting factors such as IND1, NFU1, and BOLA3.
所含基因
12 个基因