Open AccessFAF1 blocks ferroptosis by inhibiting peroxidation of polyunsaturated fatty acids
Author(s) -
Shaojie Cui,
Glenn Simmons,
Gonçalo Vale,
Yaqin Deng,
Jungyeon Kim,
Hyeonwoo Kim,
Ruihui Zhang,
Jeffrey G. McDonald,
Jin Ye
Publication year - 2022
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2107189119
Subject(s) - gpx4 , polyunsaturated fatty acid , lipid peroxidation , chemistry , biochemistry , glutathione , oxidative stress , microbiology and biotechnology , biology , enzyme , fatty acid , glutathione peroxidase
Significance The current study reveals the functions of FAF1 in protecting cells from ferroptosis, a novel cell death pathway triggered by PUFA peroxidation. In the absence of FAF1, cultured cells and mice are extremely sensitive to ferroptosis when exposed to physiological levels of PUFAs. Mechanistically, FAF1 sequesters PUFAs into the hydrophobic core of a global structure that limits their access to positively charged Fe2+ , which catalyzes the peroxidation reaction. These observations suggest that FAF1-mediated protection of PUFA peroxidation plays a critical role in preventing initiation of ferroptosis.