ArticleJournal of hepatology2020
MLKL-dependent signaling regulates autophagic flux in a murine model of non-alcohol-associated fatty liver and steatohepatitis.
Article in Journal of hepatology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 108 papers, 1 of them a synthesis that pooled it.
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Who cites it
108 citing papers in PubMed, 1 synthesis or guideline pooled it, 175 citations in OpenAlex.
- Cullin Deneddylation Suppresses the Necroptotic Pathway in Cardiomyocytes.Frontiers in physiology · 2021Pooled it
- Metabolic dysfunction-associated steatotic liver disease: pathogenic mechanisms and exercise-induced molecular adaptations.Lipids in health and disease · 2026Review
- Phosphorylation Modification Characteristics of Liver Injury-Related Proteins inPathogens (Basel, Switzerland) · 2026Article
- A Non-Canonical Role for Hepatocyte MLKL in Promoting Mitochondrial Dysfunction and Senescence in the Aging Liver.Aging cell · 2026Article
- Adipocyte caspase-8 but not RIPK3 promotes adiposity.Cell death discovery · 2026Article
- Ginsenoside F1 ameliorates nonalcoholic fatty liver disease by activating the AMPK/PGC-1α pathway and autophagy.In vitro cellular & developmental biology. Animal · 2026Article
- TOLLIP targets GSDME-NT-carrying endocytic vesicles for autophagy to regulate pyroptosis and chemotherapy efficacy.Nature cell biology · 2026Article
- Regulated necrosis at the crossroads of liver inflammation and cancer development.Nature reviews. Gastroenterology & hepatology · 2026Review
- Necroptosis induced by MLKL overexpression in liver triggers cellular senescence and leads to chronic inflammation and fibrosis.GeroScience · 2026Article
- Cadmium targeting MLKL-Drp1 axis to trigger mitochondrial oxidative stress contributes to necroinflammation in rat kidney.Journal of advanced research · 2026Article
- GATA2 deficiency exacerbates chronic liver injuryWorld journal of stem cells · 2026Article
- MLKL in liver parenchymal cells promotes liver cancer in murine metabolic dysfunction-associated steatotic liver disease.Cell death & disease · 2026Article
- Shifting cell death modes in hepatic steatosis: from apoptosis to necroptosis.Endocrine journal · 2026Review
- Targeting Programmed Cell Death in Depression: A Review of Traditional Chinese Medicine Interventions Based on Preclinical Evidence.Neuropsychiatric disease and treatment · 2026Review
- Targeting necroptosis: how does exercise protect against metabolic dysfunction-associated fatty liver disease?Frontiers in physiology · 2026Review
- Salidroside alleviates palmitic acid-induced hepatocyte injury by regulating the LILRB2-mediated autophagy pathway.In vitro cellular & developmental biology. Animal · 2026Article
- Human umbilical cord-derived mesenchymal stem cells ameliorate non-alcoholic fatty liver disease via activating TFEB-mediated autophagy in male mice.Stem cell research & therapy · 2025Article
- Hv1 inhibition rescues AD pathology by restoring microglial mitochondrial function and enhancing mitochondrial transfer.Experimental & molecular medicine · 2025Article
- Intracellular IL-24 ameliorates lipid metabolic disorders in metabolic dysfunction-associated steatohepatitis by restoring the autophagy-lysosome pathway.Cellular and molecular life sciences : CMLS · 2025Article
- METTL3-dependent mAutophagy · 2025Article
48 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
BACKGROUND &
aimsAutophagy maintains cellular homeostasis and plays a critical role in the development of non-alcoholic fatty liver and steatohepatitis. The pseudokinase mixed lineage kinase domain-like (MLKL) is a key downstream effector of receptor interacting protein kinase 3 (RIP3) in the necroptotic pathway of programmed cell death. However, recent data reveal that MLKL also regulates autophagy. Herein, we tested the hypothesis that MLKL contributes to the progression of Western diet-induced liver injury in mice by regulating autophagy.
methodsRip3
resultsThe FFC diet increased expression, phosphorylation and oligomerization of MLKL in the liver. Mlkl, but not Rip3, deficiency protected mice from FFC diet-induced liver injury. The FFC diet also induced accumulation of p62 and LC3-II, as well as markers of endoplasmic reticulum stress, in Mlkl
conclusionsTaken together, these data indicate that MLKL-dependent, but RIP3-independent, signaling contributes to FFC diet-induced liver injury by inhibiting autophagy. LAY SUMMARY: Autophagy is a regulated process that maintains cellular homeostasis. Impaired autophagy contributes to cell injury and death, thus playing a critical role in the pathogenesis of a number of diseases, including non-alcohol-associated fatty liver and steatohepatitis. Herein, we show that Mlkl-dependent, but Rip3-independent, signaling contributed to diet-induced liver injury and inflammatory responses by inhibiting autophagy. These data identify a novel co-regulatory mechanism between necroptotic and autophagic signaling pathways in non-alcoholic fatty liver disease.
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Registered trials
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.