Necroptotic MLKL attenuates autophagy following its translocation to intracellular membranes
Details
Publication Year 2019-02-11, Volume 132, Issue #5, Page pii: jcs220996
Journal Title
Journal of Cell Science
Publication Type
Journal Article
Abstract
Necroptosis is an inflammatory form of programmed cell death mediated by the pseudokinase mixed-lineage kinase domain-like protein (MLKL). Upon phosphorylation by receptor-interacting protein kinase-3 (RIPK3), MLKL oligomerizes, and translocates to and disrupts the plasma membrane, thereby causing necroptotic cell lysis. Herein, we show that activation of necroptosis in mouse dermal fibroblasts (MDFs) and HT-29 human colorectal cancer cells results in accumulation of the autophagic marker, lipidated LC3B, in an MLKL-dependent manner. Unexpectedly, the necroptosis-induced increase in lipidated LC3B was due to inhibition of autophagic flux, not the activation of autophagy. Inhibition of autophagy by MLKL correlated with a decrease in auto/lysosomal function, and required the association of activated MLKL with intracellular membranes. Collectively, our findings uncover an additional role of the MLKL pseudokinase, namely to inhibit autophagy during necroptosis.
Publisher
COB
WEHI Research Division(s)
Inflammation; Blood Cells And Blood Cancer
PubMed ID
30709919
Rights Notice
Refer to copyright notice on published article.


Creation Date: 2019-03-13 08:04:16
Last Modified: 2019-03-13 08:54:38
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