a Department of Immunology , St. Jude Children's Research Hospital , Memphis , TN , USA.
Cell Cycle. 2017 Oct 2;16(19):1748-1760. doi: 10.1080/15384101.2017.1371889. Epub 2017 Aug 30.
Necroptosis is a form of programmed necrotic cell death mediated by the kinase RIPK3 and its substrate MLKL. MLKL, which displays plasma membrane (PM) pore-forming activity upon phosphorylation, functions as the executioner during necroptosis. Thus, it was previously assumed that MLKL phosphorylation is the endpoint of the necroptotic signaling pathway. Here, we summarize several events that characterize the dying necroptotic cells after MLKL phosphorylation, including Ca influx, phosphatidylserine (PS) externalization, PM repair by ESCRT-III activation, and the final compromise of PM integrity. These processes add several unexpected regulatory events downstream of MLKL signaling. We have also observed that CoCl, which may mimic hypoxia, can induce necroptosis, which suggests that in vivo triggers of necroptosis might include a transient lack of O.
细胞程序性坏死是一种由激酶 RIPK3 和其底物 MLKL 介导的细胞坏死形式。磷酸化后的 MLKL 具有质膜（PM）孔形成活性，在细胞程序性坏死中充当执行者。因此，人们之前认为 MLKL 磷酸化是细胞程序性坏死信号通路的终点。在这里，我们总结了 MLKL 磷酸化后死亡的细胞程序性坏死的几个特征事件，包括 Ca2+内流、磷脂酰丝氨酸（PS）外翻、通过 ESCRT-III 激活修复 PM 以及 PM 完整性的最终破坏。这些过程在 MLKL 信号下游增加了几个意外的调控事件。我们还观察到，可能模拟缺氧的 CoCl2 可以诱导细胞程序性坏死，这表明细胞程序性坏死的体内触发因素可能包括短暂的 O2 缺乏。
