Emerging roles for lipids in non-apoptotic cell death.
Emerging roles for lipids in non-apoptotic cell death.
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DOI：
10.1038/cdd.2016.25
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发表时间：
2016-07
影响因子：
12.4
通讯作者：
Dixon SJ
中科院分区：
文献类型：
--
作者：
Magtanong L;Ko PJ;Dixon SJ
非凋亡调节细胞死亡（RCD）对于维持机体稳态至关重要，并且在某些病理状态下可能被异常激活。脂质正在成为多种非凋亡 RCD 途径的关键组成部分。例如，执行坏死性凋亡需要膜磷脂和成孔蛋白混合谱系激酶结构域 (MLKL) 之间的直接相互作用，而谷胱甘肽过氧化物酶 4 (GPX4) 失活后膜多不饱和脂肪酸 (PUFA) 的氧化破坏是铁死亡的必要途径。在这里，我们回顾了脂质在这些和其他形式的非凋亡细胞死亡的启动和执行中的作用。我们还考虑采用新技术，以越来越复杂的方式探讨脂质和脂质代谢在 RCD 中的作用。在某些情况下，这一新知识可能有助于开发针对脂质和脂质代谢过程的疗法，以增强或抑制特定的非凋亡 RCD 途径。
Non-apoptotic regulated cell death (RCD) is essential to maintain organismal homeostasis and may be aberrantly activated during certain pathological states. Lipids are emerging as key components of several non-apoptotic RCD pathways. For example, a direct interaction between membrane phospholipids and the pore-forming protein mixed lineage kinase domain-like (MLKL) is needed for the execution of necroptosis, while the oxidative destruction of membrane polyunsaturated fatty acids (PUFAs), following the inactivation of glutathione peroxidase 4 (GPX4), is a requisite gateway to ferroptosis. Here, we review the roles of lipids in the initiation and execution of these and other forms of non-apoptotic cell death. We also consider new technologies that are allowing for the roles of lipids and lipid metabolism in RCD to be probed in increasingly sophisticated ways. In certain cases, this new knowledge may enable the development of therapies that target lipids and lipid metabolic processes to enhance or suppress specific non-apoptotic RCD pathways.