Lipid homeostasis and regulated cell death.

Lipid homeostasis and regulated cell death.
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DOI:
10.1016/j.cbpa.2017.06.002
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发表时间:
2017-08
影响因子:
7.8
通讯作者:
Stockwell BR
Stockwell BR
中科院分区:
生物学2区
文献类型:
--
作者:
Agmon E;Stockwell BR

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现代脂质组学分析描绘了膜组织的动态图像,作为改变和适应在细胞功能中起积极作用的脂质组装。本文重点介绍了细胞膜的脂质组成如何决定特定细胞器的功能,稳态机制如何通过调节细胞膜的物理特性来维持这些功能,以及细胞如何破坏脂质稳态从而导致调节细胞死亡(RCD)。这些都是广泛的现象,这里将回顾具有代表性的例子。特别是,铁下垂(一种由脂质过氧化引起的RCD)的机制被强调,展示了脂质代谢如何驱动细胞的脂质组成向脂质氧化敏感性增加的状态。对这些相互作用的理解已经开始引起基于脂质的治疗。本文回顾了目前这种疗法的成功,并提出了未来发展的方向。
Modern lipidomics analysis paints a dynamic picture of membrane organizations, as changing and adapting lipid assemblies that play an active role in cellular function. This article highlights how the lipid composition of membranes determines specific organelle functions, how homeostatic mechanisms maintain these functions by regulating physical properties of membranes, and how cells disrupt lipid homeostasis to bring about regulated cell death (RCD). These are broad phenomena, and representative examples are reviewed here. In particular, the mechanisms of ferroptosis – a form of RCD brought about by lipid peroxidation – are highlighted, demonstrating how lipid metabolism drives cells’ lipid composition towards states of increased sensitivity to lipid oxidation. An understanding of these interactions has begun to give rise to lipid-based therapies. This article reviews current successes of such therapies, and suggests directions for future developments.
ACSL4 通过塑造细胞脂质成分来决定铁死亡敏感性。
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