Hydropersulfides inhibit lipid peroxidation and ferroptosis by scavenging radicals


erroptosis 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.

SEEK ID: https://publications.h-its.org/publications/1512

DOI: 10.1038/s41589-022-01145-w

Research Groups: Molecular Biomechanics

Publication type: Journal

Journal: Nature Chemical Biology

Publisher: Springer Science and Business Media LLC

Citation: Nature Chemical Biology 19: 28–37

Date Published: 15th Sep 2022

URL: https://www.nature.com/articles/s41589-022-01145-w

Registered Mode: manually

Authors: Uladzimir Barayeu, Danny Schilling, Mohammad Eid, Thamara Nishida Xavier da Silva, Lisa Schlicker, Nikolina Mitreska, Christopher Zapp, Frauke Gräter, Aubry K. Miller, Reinhard Kappl, Almut Schulze, José Pedro Friedmann Angeli, Tobias P. Dick

help Submitter
Barayeu, U., Schilling, D., Eid, M., Xavier da Silva, T. N., Schlicker, L., Mitreska, N., Zapp, C., Gräter, F., Miller, A. K., Kappl, R., Schulze, A., Friedmann Angeli, J. P., & Dick, T. P. (2022). Hydropersulfides inhibit lipid peroxidation and ferroptosis by scavenging radicals. In Nature Chemical Biology (Vol. 19, Issue 1, pp. 28–37). Springer Science and Business Media LLC. https://doi.org/10.1038/s41589-022-01145-w

Views: 2240

Created: 27th Sep 2022 at 09:55

Last updated: 5th Mar 2024 at 21:24

help Tags

This item has not yet been tagged.

help Attributions


Powered by
Copyright © 2008 - 2023 The University of Manchester and HITS gGmbH