Journal article
Activated MLKL attenuates autophagy following its translocation to intracellular membranes
D Frank, DL Vaux, JM Murphy, JE Vince, LM Lindqvist
Journal of Cell Science | COMPANY BIOLOGISTS LTD | Published : 2019
DOI: 10.1242/jcs.220996
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 (also known as MAP1LC3B), in an MLKL-dependent manner. Unexpectedly, the necroptosis-induced increase in lipidated LC3B was due to inhibition of autophagic flux, not the activation of autoph..
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Funding Acknowledgements
This work was supported by Australian National Health and Medical Research Council (NHMRC) Program 461221 (D.L.V.), and Project 1101405 (J.E.V.) and 1145788 (J.M.M., J.E.V. and L.M.L.) grants. J.M.M. (1105754) and J.E.V. (1141466) were supported by NHMRC Career Development Fellowships, while D.L.V. held an NHMRC Fellowship (1020136). D.F. was supported by Melbourne Research Scholarship (MRS). This work was also made possible through an Independent Research Institutes Infrastructure Support Scheme Grant (361646) from the NHMRC and a Victorian State Government Operational Infrastructure Support Grant.