Wu Zijun, Barayeu Uladzimir, Schilling Danny, Dick Tobias P, Pratt Derek A
Department of Chemistry & Biomolecular Sciences, University of Ottawa, Ottawa, Canada.
Division of Redox Regulation, DKFZ-ZMBH Alliance, German Cancer Research Center (DKFZ), Heidelberg, Germany; Faculty of Biosciences, Heidelberg University, Heidelberg, Germany.
Curr Opin Chem Biol. 2023 Oct;76:102353. doi: 10.1016/j.cbpa.2023.102353. Epub 2023 Jun 24.
Recognition of the prevalence of hydropersulfides (RSSH) and characterization of their enhanced two-electron reactivity relative to thiols have led to their implication in maintaining cellular redox homeostasis, in addition to other potential roles. Recent attention on the one-electron reactivity of RSSH has uncovered their potent radical-trapping antioxidant activity, which enables them to inhibit phospholipid peroxidation and associated cell death by ferroptosis. Herein, we briefly review key aspects of the reactivity and underlying physicochemical properties of RSSH. We emphasize their reactivity to radicals-particularly lipid peroxyl radicals that propagate the lipid peroxidation chain reaction-and the recent recognition that this results in ferroptosis suppression. We highlight open questions related to recent developments in this area and, given that all living organisms possess the ability to synthesize persulfides endogenously, suggest they may be primordial radical scavengers that occurred early in evolution and still play a role today.
对氢过硫化物（RSSH）普遍性的认识以及对其相对于硫醇增强的双电子反应性的表征，除了其他潜在作用外，还使其与维持细胞氧化还原稳态相关联。最近对RSSH单电子反应性的关注揭示了它们强大的自由基捕获抗氧化活性，这使它们能够抑制磷脂过氧化和铁死亡相关的细胞死亡。在此，我们简要回顾RSSH反应性的关键方面及其潜在的物理化学性质。我们强调它们对自由基的反应性——特别是传播脂质过氧化链反应的脂质过氧自由基——以及最近认识到这会导致铁死亡抑制。我们突出了与该领域最新进展相关的未解决问题，并且鉴于所有生物体都具有内源性合成过硫化物的能力，表明它们可能是在进化早期出现的原始自由基清除剂，至今仍发挥作用。
