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Hydropersulfides inhibit lipid peroxidation and ferroptosis by scavenging radicals.

ABSTRACT: Ferroptosis is a type of cell death caused by radical-driven lipid peroxidation, leading to membrane damage and rupture. Here we show that enzymatically produced sulfane sulfur (S⁰) species, specifically hydropersulfides, scavenge endogenously generated free radicals and, thereby, suppress lipid peroxidation and ferroptosis. By providing sulfur for S⁰ biosynthesis, cysteine can support ferroptosis resistance independently of the canonical GPX4 pathway. Our results further suggest that hydropersulfides terminate radical chain reactions through the formation and self-recombination of perthiyl radicals. The autocatalytic regeneration of hydropersulfides may explain why low micromolar concentrations of persulfides suffice to produce potent cytoprotective effects on a background of millimolar concentrations of glutathione. We propose that increased S⁰ biosynthesis is an adaptive cellular response to radical-driven lipid peroxidation, potentially representing a primordial radical protection system.

SUBMITTER: Barayeu U

PROVIDER: S-EPMC7613997 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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Hydropersulfides inhibit lipid peroxidation and ferroptosis by scavenging radicals.

Barayeu Uladzimir U Schilling Danny D Eid Mohammad M Xavier da Silva Thamara Nishida TN Schlicker Lisa L Mitreska Nikolina N Zapp Christopher C Gräter Frauke F Miller Aubry K AK Kappl Reinhard R Schulze Almut A Friedmann Angeli José Pedro JP Dick Tobias P TP

Nature chemical biology 20220915 1

Ferroptosis is a type of cell death caused by radical-driven lipid peroxidation, leading to membrane damage and rupture. Here we show that enzymatically produced sulfane sulfur (S<sup>0</sup>) species, specifically hydropersulfides, scavenge endogenously generated free radicals and, thereby, suppress lipid peroxidation and ferroptosis. By providing sulfur for S<sup>0</sup> biosynthesis, cysteine can support ferroptosis resistance independently of the canonical GPX4 pathway. Our results further s ...[more]

PMID: 36109647

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Hydropersulfides inhibit lipid peroxidation and ferroptosis by scavenging radicals.

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Hydropersulfides inhibit lipid peroxidation and ferroptosis by scavenging radicals.

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