Abstract Protein cofactors often are the business ends of proteins, and are either synthesized inside cells or are taken up from the nutrition. A cofactor that strictly needs to be synthesized by cells is the iron-sulfur (Fe/S) cluster. This evolutionary ancient compound performs numerous biochemical functions including electron transfer, catalysis, sulfur mobilization, regulation and protein stabilization. Since the discovery of eukaryotic Fe/S protein biogenesis two decades ago, more than 30 biogenesis factors have been identified in mitochondria and cytosol. They support the synthesis, trafficking and target-specific insertion of Fe/S clusters. In this review, I first summarize what led to the initial discovery of Fe/S protein biogenesis in yeast. I then discuss the function and localization of Fe/S proteins in (non-green) eukaryotes. The major part of the review provides a detailed synopsis of the three major steps of mitochondrial Fe/S protein biogenesis, i.e. the de novo synthesis of a [2Fe-2S] cluster on a scaffold protein, the Hsp70 chaperone-mediated transfer of the cluster and integration into [2Fe-2S] recipient apoproteins, and the reductive fusion of [2Fe-2S] to [4Fe-4S] clusters and their subsequent assembly into target apoproteins. Finally, I summarize the current knowledge of the mechanisms underlying the maturation of cytosolic and nuclear Fe/S proteins.

中文翻译：

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从细胞铁硫蛋白生物发生的发现到分子理解

摘要 蛋白质辅因子通常是蛋白质的商业目的，要么在细胞内合成，要么从营养中摄取。严格需要由细胞合成的辅因子是铁硫 (Fe/S) 簇。这种进化的古老化合物具有多种生化功能，包括电子转移、催化、硫动员、调节和蛋白质稳定。自 20 年前发现真核 Fe/S 蛋白生物发生以来，已经在线粒体和细胞质中鉴定了 30 多种生物发生因子。它们支持 Fe/S 簇的合成、运输和特定目标插入。在这篇综述中，我首先总结了导致酵母中 Fe/S 蛋白生物发生的初步发现的原因。然后我将讨论 Fe/S 蛋白在（非绿色）真核生物中的功能和定位。综述的主要部分提供了线粒体 Fe/S 蛋白生物发生的三个主要步骤的详细概要，即支架蛋白上 [2Fe-2S] 簇的从头合成，Hsp70 分子伴侣介导的簇转移并整合到 [2Fe-2S] 受体载脂蛋白中，以及 [2Fe-2S] 与 [4Fe-4S] 簇的还原融合以及它们随后组装成目标载脂蛋白。最后，我总结了目前关于细胞溶质和核 Fe/S 蛋白成熟机制的知识。以及 [2Fe-2S] 到 [4Fe-4S] 簇的还原融合以及它们随后组装成目标载脂蛋白。最后，我总结了目前关于细胞溶质和核 Fe/S 蛋白成熟机制的知识。以及 [2Fe-2S] 到 [4Fe-4S] 簇的还原融合以及它们随后组装成目标载脂蛋白。最后，我总结了目前关于细胞溶质和核 Fe/S 蛋白成熟机制的知识。