Egozi Shany, Ast Tslil
Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot, Israel.
Metallomics. 2025 Jul 9;17(7). doi: 10.1093/mtomcs/mfaf022.
Iron-sulfur (Fe-S) clusters are ancient and versatile cofactors that drive essential cellular functions, from electron transport to enzyme catalysis. Their intrinsic sensitivity to oxidation has shaped the evolution of specialized Fe-S cluster biosynthetic and protective mechanisms. Recent findings highlight how human Fe-S-binding regulators exploit this cofactor's reactivity to sense iron and oxygen levels, translating environmental cues into appropriate homeostatic responses. Yet, the same redox sensitivity also renders Fe-S cluster proteins and biosynthesis particularly vulnerable to high oxygen tensions, contributing to pathological outcomes. In this minireview, we examine key discoveries illustrating how Fe-S clusters and oxygen intersect to influence both human health and disease. Finally, we discuss how identifying novel Fe-S targets and regulatory circuits may open innovative therapeutic avenues-harnessing oxygen itself as a strategic element in managing relevant disorders.
铁硫（Fe-S）簇是古老且多功能的辅因子，驱动着从电子传递到酶催化等基本细胞功能。它们对氧化的内在敏感性塑造了专门的Fe-S簇生物合成和保护机制的进化。最近的研究结果突出了人类Fe-S结合调节因子如何利用这种辅因子的反应性来感知铁和氧水平，将环境线索转化为适当的稳态反应。然而，同样的氧化还原敏感性也使Fe-S簇蛋白和生物合成特别容易受到高氧张力的影响，从而导致病理结果。在这篇小型综述中，我们研究了一些关键发现，这些发现阐明了Fe-S簇与氧如何相互作用以影响人类健康和疾病。最后，我们讨论了识别新的Fe-S靶点和调节回路如何可能开辟创新的治疗途径——将氧本身作为管理相关疾病的战略要素加以利用。
