Unsolved mysteries: How does lipid peroxidation cause ferroptosis?

Unsolved mysteries: How does lipid peroxidation cause ferroptosis?
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DOI:
10.1371/journal.pbio.2006203
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发表时间:
2018-05
期刊:
影响因子:
9.8
通讯作者:
Stockwell BR
Stockwell BR
中科院分区:
生物学1区
文献类型:
--
作者:
Feng H;Stockwell BR

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亚铁凋亡是一种细胞死亡过程,由细胞膜损伤驱动,与许多人类疾病有关。铁缺乏症是由负责修复细胞膜氧化损伤的关键酶谷胱甘肽过氧化物酶4(GPX 4)的活性丧失引起的。GPX 4通常会去除铁依赖性脂质过氧化的危险产物,保护细胞膜免受此类损伤;当GPX 4失效时,就会发生铁细胞凋亡。铁凋亡不同于凋亡、坏死性凋亡、坏死和其他细胞死亡模式。关于细胞在铁凋亡过程中如何死亡的几个关键谜团仍然没有解决。首先,脂质过氧化的驱动因素尚不清楚。其次,致死性脂质过氧化物的亚细胞定位仍然是一个悬而未决的问题。最后,脂质过氧化究竟如何导致细胞死亡是一个未解之谜。这些问题的答案将提供深入了解铁凋亡细胞死亡和相关的人类疾病的机制,以及这些疾病的新的治疗策略。
Ferroptosis is a cell death process driven by damage to cell membranes and linked to numerous human diseases. Ferroptosis is caused by loss of activity of the key enzyme that is tasked with repairing oxidative damage to cell membranes—glutathione peroxidase 4 (GPX4). GPX4 normally removes the dangerous products of iron-dependent lipid peroxidation, protecting cell membranes from this type of damage; when GPX4 fails, ferroptosis ensues. Ferroptosis is distinct from apoptosis, necroptosis, necrosis, and other modes of cell death. Several key mysteries regarding how cells die during ferroptosis remain unsolved. First, the drivers of lipid peroxidation are not yet clear. Second, the subcellular location of lethal lipid peroxides remains an outstanding question. Finally, how exactly lipid peroxidation leads to cell death is an unsolved mystery. Answers to these questions will provide insights into the mechanisms of ferroptotic cell death and associated human diseases, as well as new therapeutic strategies for such diseases.
ACSL4 通过塑造细胞脂质成分来决定铁死亡敏感性。
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