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dc.contributor.authorSamali, Afshin
dc.identifier.citationSaveljeva, S,Mc Laughlin, SL,Vandenabeele, P,Samali, A,Bertrand, MJM (2015) 'Endoplasmic reticulum stress induces ligand-independent TNFR1-mediated necroptosis in L929 cells'. Cell Death & Disease, 6 .en_US
dc.descriptionJournal articleen_US
dc.description.abstractEndoplasmic reticulum (ER) stress-induced cellular dysfunction and death is associated with several human diseases. It has been widely reported that ER stress kills through activation of the intrinsic mitochondrial apoptotic pathway. Here we demonstrate that ER stress can also induce necroptosis, an receptor-interacting protein kinase 1 (RIPK1)/RIPK3/mixed lineage kinase domain-like protein (MLKL)-dependent form of necrosis. Remarkably, we observed that necroptosis induced by various ER stressors in L929 cells is dependent on tumor necrosis factor receptor 1 (TNFR1), but occurs independently of autocrine TNF or lymphotoxin a production. Moreover, we found that repression of either TNFR1, RIPK1 or MLKL did not protect the cells from death but instead allowed a switch to ER stress-induced apoptosis. Interestingly, while caspase inhibition was sufficient to protect TNFR1- or MLKL-deficient cells from death, rescue of the RIPK1-deficient cells additionally required RIPK3 depletion, indicating a switch back to RIPK3-dependent necroptosis in caspase-inhibited conditions. The finding that ER stress also induces necroptosis may open new therapeutic opportunities for the treatment of pathologies resulting from unresolved ER stress.en_US
dc.relation.ispartofCell Death & Diseaseen
dc.titleEndoplasmic reticulum stress induces ligand-independent TNFR1-mediated necroptosis in L929 cellsen_US
dc.local.contactAfshin Samali, Bioscience Research Building, North Campus, Nui Galway. 2440 Email:
dc.local.copyrightcheckedYes This is a fully open access journal. I have paid for the license.

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