Exogenous Monounsaturated Fatty Acids Promote a Ferroptosis-Resistant Cell State
Exogenous Monounsaturated Fatty Acids Promote a Ferroptosis-Resistant Cell State
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DOI：
10.1016/j.chembiol.2018.11.016
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发表时间：
2019-03-21
影响因子：
8.6
通讯作者：
Dixon, Scott J.
中科院分区：
文献类型：
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作者：
Magtanong, Leslie;Ko, Pin-Joe;Dixon, Scott J.
细胞死亡的启动和执行可以受到多种脂质的调节。环境(外源性)脂的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)能有效地抑制铁性下垂的非凋亡性、铁依赖性、氧化性细胞死亡过程。这种保护作用与抑制脂质活性氧物种(ROS)在质膜上的积累和降低含有可氧化多不饱和脂肪酸的磷脂水平有关。外源MUFAs处理可降低质膜脂对几个小时内氧化的敏感性。这种作用需要酰基辅酶A合成酶长链家族成员3(ACSL3)激活MUFA，并且不依赖于脂滴的形成。外源性MUFA也可以保护细胞免受饱和脂肪酸积累引起的细胞凋亡脂毒性的影响，但这种保护方式不依赖于ACSL3。我们的工作表明，依赖ACSL3的MUFA激活促进了一种抗铁下垂的细胞状态。
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.