Although apoptosis has long dominated the spotlight, studies in the past two decades have expanded the repertoire of programmed cell death (PCD). Several forms of non-apoptotic regulated cell death have been identified, with important links to organismal homeostasis and different disease pathologies. Necroptosis, ferroptosis, pyroptosis, and NETosis are the major forms of PCD that have attracted attention. Clear biochemical distinctions differentiate these forms of non-apoptotic PCD at the protein and membrane levels. For instance, pore formation at the plasma membrane is a hallmark of necroptosis and pyroptosis; however, different proteins facilitate pore formation in these processes. Here, we will highlight the role of lipids in different forms of non-apoptotic PCD. In particular, we discuss how lipids can trigger or facilitate the membrane-related changes that result in cell death. We also highlight the use of small molecules in elucidating the mechanisms of non-apoptotic PCD and the potential of lipid biosynthetic pathways to perturb these processes for therapeutic applications as a future avenue of research.

中文翻译：

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聚焦非凋亡细胞死亡中的脂质

尽管细胞凋亡长期以来一直是人们关注的焦点，但是在过去的二十年中，研究已经扩大了程序性细胞死亡（PCD）的范围。已经确定了几种形式的非凋亡调节性细胞死亡，它们与机体动态平衡和不同的疾病病理学有着重要的联系。坏死病，肥大病，发烧病和NETosis是引起人们关注的PCD的主要形式。明显的生化差异在蛋白质和膜水平上区分了这些形式的非凋亡PCD。例如，质膜上的孔形成是坏死病和发烧的标志。然而，不同的蛋白质在这些过程中促进了孔的形成。在这里，我们将重点介绍脂质在不同形式的非凋亡PCD中的作用。尤其是，我们讨论了脂质如何触发或促进导致细胞死亡的膜相关变化。我们还强调了使用小分子阐明非凋亡PCD的机制以及脂质生物合成途径扰动这些过程用于治疗应用的潜力，作为未来的研究途径。