Exogenous Monounsaturated Fatty Acids Promote a Ferroptosis-Resistant Cell State

被引：810

作者：

Magtanong, Leslie ^{[1
]}

Ko, Pin-Joe ^{[1
]}

To, Milton ^{[2
]}

Cao, Jennifer Yinuo ^{[1
]}

Forcina, Giovanni C. ^{[1
]}

Tarangelo, Amy ^{[1
]}

Ward, Carl C. ^{[3
,4
]}

Cho, Kevin ^{[5
,6
]}

Patti, Gary J. ^{[5
,6
]}

Nomura, Daniel K. ^{[2
,3
,4
]}

Olzmann, James A. ^{[2
]}

Dixon, Scott J. ^{[1
]}

机构：

[1] Stanford Univ, Dept Biol, Stanford, CA 94305 USA

[2] Univ Calif Berkeley, Dept Nutr Sci & Toxicol, Berkeley, CA 94720 USA

[3] Univ Calif Berkeley, Dept Chem, Berkeley, CA 94720 USA

[4] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA

[5] Washington Univ, Dept Chem, St Louis, MO 63130 USA

[6] Washington Univ, Dept Med, St Louis, MO 63130 USA

来源：

CELL CHEMICAL BIOLOGY | 2019年 / 26卷 / 03期

关键词：

ACYL-COA SYNTHETASE; CANCER-CELLS; METABOLISM; INHIBITOR; OXIDATION; LIPIDS; PEROXIDATION; SENSITIVITY; PROTECTS; ROLES;

D O I：

10.1016/j.chembiol.2018.11.016

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The initiation and execution of cell death can be regulated by various lipids. How the levels of environmental (exogenous) lipids impact cell death sensitivity is not well understood. We find that exogenous monounsaturated fatty acids (MUFAs) potently inhibit the non-apoptotic, iron-dependent, oxidative cell death process of ferroptosis. This protective effect is associated with the suppression of lipid reactive oxygen species (ROS) accumulation at the plasma membrane and decreased levels of phospholipids containing oxidizable polyunsaturated fatty acids. Treatment with exogenous MUFAs reduces the sensitivity of plasma membrane lipids to oxidation over several hours. This effect requires MUFA activation by acyl-coenzyme A synthetase long-chain family member 3 (ACSL3) and is independent of lipid droplet formation. Exogenous MUFAs also protect cells from apoptotic lipotoxicity caused by the accumulation of saturated fatty acids, but in an ACSL3-independent manner. Our work demonstrates that ACSL3-dependent MUFA activation promotes a ferroptosis-resistant cell state.

引用

页码：420 / +

页数：22

共 46 条

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