How do different lipid peroxidation mechanisms contribute to ferroptosis?
How do different lipid peroxidation mechanisms contribute to ferroptosis?
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DOI：
10.1016/j.xcrp.2023.101683
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发表时间：
2023-11
期刊：
影响因子：
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通讯作者：
Quynh Do;Libin Xu
中科院分区：
文献类型：
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作者：
Quynh Do;Libin Xu
脂质过氧化是铁死亡细胞死亡的驱动因素。然而，非共轭和共轭多不饱和脂肪酸以不同的方式增强铁死亡，而一些类异戊二烯衍生的脂质尽管具有高度氧化性，但仍能抑制铁死亡。从这个角度来看，我们认为不同的氧化机制和产物导致脂质在调节铁死亡方面的效力存在差异。我们首先讨论各种脂质对两种决定速率的自由基传播机制（氢原子转移（HAT）和过氧自由基加成（PRA））的相对反应性，以及由此产生的差异产物谱。然后，我们讨论了脂质过氧化在铁死亡中的作用和调节，以及不同氧化产物（例如截短脂质和脂质亲电子试剂）从 HAT 和 PRA 机制到铁死亡执行的潜在贡献。最后，我们对剩下的问题提出了我们的观点，以充分理解从脂质过氧化到铁死亡的过程。
Lipid peroxidation is the driver of ferroptotic cell death. However, nonconjugated and conjugated polyunsaturated fatty acids potentiate ferroptosis differently, while some isoprenoid-derived lipids inhibit ferroptosis despite being highly oxidizable. In this perspective, we propose that different oxidation mechanisms and products contribute to the discrepancies in the lipids' potency in modulating ferroptosis. We first discuss the relative reactivities of various lipids toward two rate-determining free radical propagating mechanisms, hydrogen atom transfer (HAT) and peroxyl radical addition (PRA), and the resulting differential product profiles. We then discuss the role and regulation of lipid peroxidation in ferroptosis and the potential contributions of different oxidation products, such as truncated lipids and lipid electrophiles, from HAT and PRA mechanisms to the execution of ferroptosis. Lastly, we offer our perspective on the remaining questions to fully understand the process from lipid peroxidation to ferroptosis.