RIP3: a molecular switch for necrosis and inflammation.
TLDR
The current understanding of the mechanisms that drive RIP3-dependent necrosis and its role in different inflammatory diseases is reviewed.Abstract:
The receptor-interacting protein kinase 3 (RIP3/RIPK3) has emerged as a critical regulator of programmed necrosis/ necroptosis, an inflammatory form of cell death with important functions in pathogen-induced and sterile inflammation. RIP3 activation is tightly regulated by phosphorylation, ubiquitination, and caspase-mediated cleavage. These post-translational modifications coordinately regulate the assembly of a macromolecular signaling complex termed the necrosome. Recently, several reports indicate that RIP3 can promote inflammation independent of its pronecrotic activity. Here, we review our current understanding of the mechanisms that drive RIP3-dependent necrosis and its role in different inflammatory diseases.read more
Citations
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Regulated necrosis: the expanding network of non-apoptotic cell death pathways
Tom Vanden Berghe,Andreas Linkermann,Sandrine Jouan-Lanhouet,Henning Walczak,Peter Vandenabeele +4 more
TL;DR: Elucidating how these pathways of regulated necrosis are interconnected at the molecular level should enable this process to be therapeutically targeted.
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Mixed Lineage Kinase Domain-like Protein MLKL Causes Necrotic Membrane Disruption upon Phosphorylation by RIP3
TL;DR: The development of a monoclonal antibody that specifically recognizes phosphorylated MLKL in cells dying of this pathway and in human liver biopsy samples from patients suffering from drug-induced liver injury is reported.
Journal ArticleDOI
Glutaminolysis and Transferrin Regulate Ferroptosis.
TL;DR: Inhibition of glutaminolysis, the essential component of ferroptosis, can reduce heart injury triggered by ischemia/reperfusion, suggesting a potential therapeutic approach for treating related diseases.
Journal ArticleDOI
Ferroptosis is an autophagic cell death process
TL;DR: It is reported that inhibition of ferritinophagy by blockage of autophagy or knockdown of NCOA4 abrogated the accumulation of ferroptosis-associated cellular labile iron and reactive oxygen species, as well as eventual ferroPTotic cell death.
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Caspase-1-induced pyroptosis is an innate immune effector mechanism against intracellular bacteria (111.33)
Edward A. Miao,Irina A. Leaf,Piper M. Treuting,Dat P. Mao,Anasuya Sarkar,Mark D. Wewers,Alan Aderem +6 more
TL;DR: It is demonstrated that activation of caspase-1 clears intracellular bacteria in vivo independently of IL-1β and IL-18 and establishes pyroptosis as an efficient mechanism of bacterial clearance by the innate immune system.
References
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Caspase-8 Serves Both Apoptotic and Nonapoptotic Roles
Tae Bong Kang,Tehila Ben-Moshe,Eugene Varfolomeev,Yael Pewzner-Jung,Nir Yogev,Anna Jurewicz,Ari Waisman,Ori Brenner,Rebecca Haffner,Erika Gustafsson,Parameswaran Ramakrishnan,Tsvee Lapidot,David Wallach +12 more
TL;DR: Caspase-8 deletion in bone-marrow cells resulted in arrest of hemopoietic progenitor functioning, and in cells of the myelomonocytic lineage, its deletion led to arrest of differentiation into macrophages and to cell death.
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Caspase-8 blocks kinase RIPK3-mediated activation of the NLRP3 inflammasome.
TL;DR: An activity of caspase-8 in dendritic cells that controls the initiation of inflammation in another way is described, providing new insight into potentially pathological inflammatory processes to which RIPK1- and RIPK3-mediated signaling contributes.
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Many stimuli pull the necrotic trigger, an overview
TL;DR: The observation that RIPK3 ablation rescues embryonic lethality in mice deficient in caspase-8 or Fas-associated-protein-via-a-death-domain demonstrates the crucial role of this apoptotic platform in the negative control of necroptosis during development.
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Anthrax lethal toxin and Salmonella elicit the common cell death pathway of caspase-1-dependent pyroptosis via distinct mechanisms
TL;DR: It is demonstrated that distinct activation pathways elicit the conserved cell death effector mechanism of caspase-1-mediated pyroptosis and support the notion that this pathway of proinflammatory programmed cell death is broadly relevant to cell death and inflammation invoked by diverse stimuli.
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Apoptosis induced by the toll-like receptor adaptor TRIF is dependent on its receptor interacting protein homotypic interaction motif.
TL;DR: The ability of TRIF to induce apoptosis was not dependent on its ability to activate either IFN regulatory factor-3 or NF-κB but was dependent on the presence of an intact RHIM, and deletion and mutational analyses revealed that the RHIM in TRIF was essential for TRif-induced apoptosis and contributed to TRIF-induced NF-β activation.