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.
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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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Journal ArticleDOI
FADD: Essential for Embryo Development and Signaling from Some, But Not All, Inducers of Apoptosis
Wen-Chen Yeh,José Luis de la Pompa,Mila E. McCurrach,Hong-Bing Shu,Andrew J. Elia,Arda Shahinian,Michelle Ng,Andrew Wakeham,Wilson Khoo,Kyran O. Mitchell,Wafik S. El-Deiry,Scott W. Lowe,David V. Goeddel,Tak W. Mak +13 more
TL;DR: CD95, tumor necrosis factor receptor type 1 (TNFR-1), and death receptor 3 (DR3) did not induce apoptosis in FADD-deficient embryonic fibroblasts, whereas DR4, oncogenes E1A and c-myc, and chemotherapeutic agent adriamycin did.
Journal Article
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.
Journal ArticleDOI
The Mitochondrial Phosphatase PGAM5 Functions at the Convergence Point of Multiple Necrotic Death Pathways
TL;DR: PGAM5 was defined as the convergent point for multiple necrosis pathways after it was identified that upon necrosis induction, PGAM5S recruited the mitochondrial fission factor Drp1 and activated its GTPase activity by dephosphorylating the serine 637 site of Drp 1.
Journal ArticleDOI
Linear ubiquitination prevents inflammation and regulates immune signalling
Björn Gerlach,Stefanie M. Cordier,Anna C. Schmukle,Christoph H. Emmerich,Christoph H. Emmerich,Eva Rieser,Tobias L. Haas,Andrew I. Webb,James A Rickard,Holly Anderton,W. Wei-Lynn Wong,Ueli Nachbur,Lahiru Gangoda,Uwe Warnken,Anthony W. Purcell,John Silke,Henning Walczak,Henning Walczak +17 more
TL;DR: It is concluded that by enabling linear ubiquitination in the TNF receptor signalling complex, SHARPIN interferes with TNF-induced cell death and, thereby, prevents inflammation.
Journal ArticleDOI
RIP1 is an essential mediator of Toll-like receptor 3-induced NF-kappa B activation.
Etienne Meylan,Kim Burns,Kay Hofmann,Vincent Blancheteau,Fabio Martinon,Michelle A. Kelliher,Jürg Tschopp +6 more
TL;DR: This work investigated the 'downstream' signaling events that regulate TLR3-dependent Trif-induced NF-κB activation and found that RIP1 mediates Trif -RIP1–inducedNF-κBs activation.