FAF1 blocks ferroptosis by inhibiting peroxidation of polyunsaturated fatty acids

Shaojie Cui; Glenn Simmons; Goncalo Vale; Yaqin Deng; Jungyeon Kim; Hyeonwoo Kim; Ruihui Zhang; Jeffrey G. McDonald; Jin Ye

doi:10.1073/pnas.2107189119

FAF1 blocks ferroptosis by inhibiting peroxidation of polyunsaturated fatty acids

Shaojie Cui, Glenn Simmons, Goncalo Vale, Yaqin Deng, Jungyeon Kim, Hyeonwoo Kim, Ruihui Zhang, Jeffrey G. McDonald, Jin Ye

Research output: Contribution to journal › Article › peer-review

Abstract

SignificanceThe 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.

Original language	English (US)
Pages (from-to)	e2107189119
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	119
Issue number	17
DOIs	https://doi.org/10.1073/pnas.2107189119
State	Published - Apr 26 2022

Keywords

FAF1
ferroptosis
polyunsaturated fatty acids

ASJC Scopus subject areas

General

Access to Document

10.1073/pnas.2107189119

Cite this

FAF1 blocks ferroptosis by inhibiting peroxidation of polyunsaturated fatty acids. / Cui, Shaojie; Simmons, Glenn; Vale, Goncalo; Deng, Yaqin; Kim, Jungyeon; Kim, Hyeonwoo; Zhang, Ruihui; McDonald, Jeffrey G.; Ye, Jin.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 119, No. 17, 26.04.2022, p. e2107189119.

Research output: Contribution to journal › Article › peer-review

@article{fb431a4a4f65419e8875c33cbf98f538,

title = "FAF1 blocks ferroptosis by inhibiting peroxidation of polyunsaturated fatty acids",

abstract = "SignificanceThe 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.",

keywords = "FAF1, ferroptosis, polyunsaturated fatty acids",

author = "Shaojie Cui and Glenn Simmons and Goncalo Vale and Yaqin Deng and Jungyeon Kim and Hyeonwoo Kim and Ruihui Zhang and McDonald, {Jeffrey G.} and Jin Ye",

year = "2022",

month = apr,

day = "26",

doi = "10.1073/pnas.2107189119",

language = "English (US)",

volume = "119",

pages = "e2107189119",

journal = "Proceedings of the National Academy of Sciences of the United States of America",

issn = "0027-8424",

publisher = "National Academy of Sciences",

number = "17",

}

TY - JOUR

T1 - FAF1 blocks ferroptosis by inhibiting peroxidation of polyunsaturated fatty acids

AU - Cui, Shaojie

AU - Simmons, Glenn

AU - Vale, Goncalo

AU - Deng, Yaqin

AU - Kim, Jungyeon

AU - Kim, Hyeonwoo

AU - Zhang, Ruihui

AU - McDonald, Jeffrey G.

AU - Ye, Jin

PY - 2022/4/26

Y1 - 2022/4/26

N2 - SignificanceThe 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.

AB - SignificanceThe 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.

KW - FAF1

KW - ferroptosis

KW - polyunsaturated fatty acids

UR - http://www.scopus.com/inward/record.url?scp=85128863418&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85128863418&partnerID=8YFLogxK

U2 - 10.1073/pnas.2107189119

DO - 10.1073/pnas.2107189119

M3 - Article

C2 - 35467977

AN - SCOPUS:85128863418

VL - 119

SP - e2107189119

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 17

ER -

FAF1 blocks ferroptosis by inhibiting peroxidation of polyunsaturated fatty acids

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this