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Cell Cycle. 2017 Oct 2;16(19):1748-1760. doi: 10.1080/15384101.2017.1371889. Epub 2017 Aug 30.

Biological events and molecular signaling following MLKL activation during necroptosis.

Author information

1
a Department of Immunology , St. Jude Children's Research Hospital , Memphis , TN , USA.

Abstract

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 Ca2+ 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 CoCl2, which may mimic hypoxia, can induce necroptosis, which suggests that in vivo triggers of necroptosis might include a transient lack of O2.

KEYWORDS:

ESCRT; MLKL; Necroptosis; RIPK3; cell death; plasma membrane repair

PMID:
28854080
PMCID:
PMC5628637
DOI:
10.1080/15384101.2017.1371889
[Indexed for MEDLINE]
Free PMC Article

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