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Characterization of MLKL-mediated Plasma Membrane Rupture in Necroptosis
08:55

Characterization of MLKL-mediated Plasma Membrane Rupture in Necroptosis

Published on: August 7, 2018

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Biological events and molecular signaling following MLKL activation during necroptosis

Yi-Nan Gong1, Cliff Guy1, Jeremy Chase Crawford1

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

Cell Cycle (Georgetown, Tex.)
|August 31, 2017
PubMed

Insights

Necroptosis, a programmed cell death, involves MLKL executioner activity. New findings reveal crucial events after MLKL phosphorylation, including cell membrane repair and potential hypoxia triggers.

Area of Science:

  • Cellular Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Necroptosis is a programmed cell death pathway regulated by RIPK3 and MLKL.
  • MLKL phosphorylation initiates plasma membrane pore formation, previously thought to be the terminal event.

Purpose of the Study:

  • To elucidate the events occurring downstream of MLKL phosphorylation during necroptosis.
  • To identify potential in vivo triggers of necroptosis, such as hypoxia.

Main Methods:

  • Review and summarization of existing literature on necroptosis signaling.
  • Observation of cellular events following MLKL phosphorylation.
  • Investigation of Cobalt chloride (CoCl2) as a potential inducer of necroptosis.

Main Results:

  • MLKL phosphorylation is followed by significant cellular events: Ca2+ influx, phosphatidylserine externalization, and ESCRT-III mediated plasma membrane repair.
  • Despite repair attempts, plasma membrane integrity is ultimately compromised.
  • Cobalt chloride, mimicking hypoxia, was observed to induce necroptosis.

Conclusions:

  • MLKL phosphorylation is not the endpoint; several regulatory events occur downstream, impacting cell death.
  • Hypoxia or transient oxygen deprivation may serve as in vivo triggers for necroptosis.
Keywords:
ESCRTMLKLNecroptosisRIPK3cell deathplasma membrane repair

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