外源性单不饱和脂肪酸促进了铁死亡抗性细胞状态。
Exogenous Monounsaturated Fatty Acids Promote a Ferroptosis-Resistant Cell State.
机构信息
Department of Biology, Stanford University, Stanford, CA 94305, USA.
Department of Nutritional Sciences and Toxicology, University of California, Berkeley, Berkeley, CA 94720, USA.
出版信息
Cell Chem Biol. 2019 Mar 21;26(3):420-432.e9. doi: 10.1016/j.chembiol.2018.11.016. Epub 2019 Jan 24.
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.
细胞死亡的启动和执行可以受到各种脂质的调控。环境（外源性）脂质水平如何影响细胞死亡敏感性尚不清楚。我们发现，外源性单不饱和脂肪酸（MUFAs）强烈抑制非凋亡、铁依赖性、氧化细胞死亡过程的铁死亡。这种保护作用与抑制质膜上脂质活性氧（ROS）的积累以及含有可氧化多不饱和脂肪酸的磷脂水平降低有关。外源性 MUFAs 的处理在数小时内降低了质膜脂质对氧化的敏感性。这种效应需要酰基辅酶 A 合成酶长链家族成员 3（ACSL3）激活 MUFAs，并且不依赖于脂滴形成。外源性 MUFAs 还可以保护细胞免受饱和脂肪酸积累引起的凋亡性脂肪毒性，但不依赖于 ACSL3。我们的工作表明，ACSL3 依赖性 MUFAs 激活促进了铁死亡抵抗的细胞状态。
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