ArticleThe Journal of clinical investigation2016
The pseudokinase MLKL mediates programmed hepatocellular necrosis independently of RIPK3 during hepatitis.
Article in The Journal of clinical investigation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 papers.
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Who cites it
95 citing papers in PubMed, 154 citations in OpenAlex.
- Review
- TNK1 is a targetable JAK-independent driver of STAT signaling and inflammation.Genes & development · 2026Article
- Regulated necrosis at the crossroads of liver inflammation and cancer development.Nature reviews. Gastroenterology & hepatology · 2026Review
- MLKL-Mediated Necroptosis Predominantly Contributes to Immune-Associated Myocardial Damage.Inflammation · 2025Article
- Defects in the necroptosis machinery are a cancer resistance mechanism to checkpoint inhibitor immunotherapy.Journal for immunotherapy of cancer · 2025Article
- Harnessing the FGFR2/NF2/YAP signaling-dependent necroptosis to develop an FGFR2/IL-8 dual blockade therapeutic strategy.Nature communications · 2025Article
- Mixed lineage kinase domain-like protein deficiency exacerbates early injury in a mouse model of acetaminophen hepatotoxicity.Toxicological sciences : an official journal of the Society of Toxicology · 2025Article
- Targeting mixed lineage kinase domain-like protein's non-necroptosis role: A new horizon in anti-inflammatory therapy for alcoholic liver disease.World journal of gastroenterology · 2025Article
- MSCs Suppress Macrophage Necroptosis and Foster Liver Regeneration by Modulating SP1/SK1 Axis in Treating Acute Severe Autoimmune Hepatitis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Divergent roles of RIPK3 and MLKL in high-fat diet-induced obesity and MAFLD in mice.Life science alliance · 2025Article
- RIPK1 in necroptosis and recent progress in related pharmaceutics.Frontiers in immunology · 2025Review
- MLKL promotes hepatocarcinogenesis through inhibition of AMPK-mediated autophagy.Cell death and differentiation · 2024Article
- Acute liver failure: A clinically severe syndrome characterized by intricate mechanisms.World journal of hepatology · 2024Article
- Spatiotemporal Control of Inflammatory Lytic Cell Death Through Optogenetic Induction of RIPK3 Oligomerization.Journal of molecular biology · 2024Article
- Pervasive loss of regulated necrotic cell death genes in elephants, hyraxes, and sea cows (bioRxiv : the preprint server for biology · 2024Article
- Mediators of necroptosis: from cell death to metabolic regulation.EMBO molecular medicine · 2024Review
- Non-canonical BIM-regulated energy metabolism determines drug-induced liver necrosis.Cell death and differentiation · 2024Article
- Polarity protein AF6 functions as a modulator of necroptosis by regulating ubiquitination of RIPK1 in liver diseases.Cell death & disease · 2023Article
- UDP-glucuronate metabolism controls RIPK1-driven liver damage in nonalcoholic steatohepatitis.Nature communications · 2023Article
- Necroptosis of macrophage is a key pathological feature in biliary atresia via GDCA/S1PR2/ZBP1/p-MLKL axis.Cell death & disease · 2023Article
35 more citing papers are in PubMed but not listed here.
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Authors and funding
15 authors at 7 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although necrosis and necroinflammation are central features of many liver diseases, the role of programmed necrosis in the context of inflammation-dependent hepatocellular death remains to be fully determined. Here, we have demonstrated that the pseudokinase mixed lineage kinase domain-like protein (MLKL), which plays a key role in the execution of receptor-interacting protein (RIP) kinase-dependent necroptosis, is upregulated and activated in human autoimmune hepatitis and in a murine model of inflammation-dependent hepatitis. Using genetic and pharmacologic approaches, we determined that hepatocellular necrosis in experimental hepatitis is driven by an MLKL-dependent pathway that occurs independently of RIPK3. Moreover, we have provided evidence that the cytotoxic activity of the proinflammatory cytokine IFN-γ in hepatic inflammation is strongly connected to induction of MLKL expression via activation of the transcription factor STAT1. In summary, our results reveal a pathway for MLKL-dependent programmed necrosis that is executed in the absence of RIPK3 and potentially drives the pathogenesis of severe liver diseases.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.