ArticleCell death discovery2023
MLKL deficiency attenuated hepatocyte oxidative DNA damage by activating mitophagy to suppress macrophage cGAS-STING signaling during liver ischemia and reperfusion injury.
Article in Cell death discovery, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
27 citing papers in PubMed, 34 citations in OpenAlex.
- The cGAS-STING/MITA pathway in innate antiviral immunity and beyond.Cell insight · 2026Review
- Genomic Stress and DNA Repair During Macrophage Differentiation and Inflammatory Activation.International journal of molecular sciences · 2026Review
- A Non-Canonical Role for Hepatocyte MLKL in Promoting Mitochondrial Dysfunction and Senescence in the Aging Liver.Aging cell · 2026Article
- Mitophagy in Hepatic Ischemia-Reperfusion Injury: From Mitochondrial Dysfunction to Therapeutic Targeting.Biomolecules · 2026Review
- Targeting cGAS-STING signaling to overcome antibiotic-resistant bacterial infections: Challenges and opportunities.Science advances · 2026Review
- Mitochondrial DNA regulation of hepatic ischemia-reperfusion injury and intervention strategies.Journal of translational medicine · 2026Review
- TNFAIP3 and MLKL-Related Necroptosis Signatures in Liver Transplant Ischemia-Reperfusion Injury: Integrated Transcriptomic and Experimental Evidence.Journal of inflammation research · 2026Article
- Sterile Inflammation and Cell Death Pathways in Liver Ischemia-Reperfusion Injury: A Review and Perspective.Endocrine, metabolic & immune disorders drug targets · 2026Review
- Bimodal regulation and precision therapy of neutrophil extracellular traps in liver ischemia-reperfusion injury: recent advances.Frontiers in immunology · 2026Review
- Mitochondrial dysfunction in immune cells during the perioperative period: mechanisms, emerging therapeutic strategies, and implications for multi-organ protection.Frontiers in immunology · 2026Review
- Necroptotic cell death consequences and disease relevance.Nature immunology · 2025Review
- Obesity-Driven Metabolic Disorders: The Interplay of Inflammation and Mitochondrial Dysfunction.International journal of molecular sciences · 2025Review
- Liver X Receptor Activation Alleviates Hepatic Ischemia-Reperfusion Injury in Diabetes by Inhibiting NF-κB-NLRP3 Activation.Immunity, inflammation and disease · 2025Article
- Impact of Mlkl or Ripk3 deletion on age-associated liver inflammation, metabolic health, and lifespan.GeroScience · 2025Article
- Mixed lineage kinase domain-like protein in liver diseases: Cell-type-specific functions and dual roles.World journal of gastroenterology · 2025Article
- Cytosolic nucleic acid sensing as driver of critical illness: mechanisms and advances in therapy.Signal transduction and targeted therapy · 2025Review
- Inflammatory adhesion mediates myocardial segmental necroptosis induced by mixed lineage kinase domain-like protein in acute myocardial infarction.Cell communication and signaling : CCS · 2025Article
- cGAS-STING Targeting Offers Novel Therapeutic Opportunities in Liver Diseases.Drug design, development and therapy · 2025Review
- MLKL as an emerging machinery for modulating organelle dynamics: regulatory mechanisms, pathophysiological significance, and targeted therapeutics.Frontiers in pharmacology · 2025Review
- Novel Perspectives in Hepatic Ischemia-Reperfusion Injury: The cGAS-STING Pathway.Journal of inflammation research · 2025Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 3 countries.
Funding
Abstract
Mixed-lineage kinase domain-like protein (MLKL)-mediated necroptosis has been implicated in aggravating liver ischemia and reperfusion (IR) injury. However, the precise role and mechanism of MLKL in regulating oxidative DNA damage of hepatocytes and subsequent activation of macrophage stimulator of interferon genes (STING) signaling remains unclear. In this study, we investigated the role of MLKL in regulating the interplay between hepatocyte injury and macrophage pro-inflammatory responses during liver IR injury. We found that IR increased MLKL expression in liver tissues of wild type (WT) mice. MLKL knockout (KO) attenuated liver IR injury and suppressed the activation of cGAS-STING signaling in intrahepatic macrophages, which was abrogated by STING activation with its agonist. Mechanistically, IR induced oxidative DNA damage in hepatocytes, leading to cGAS-STING activation in macrophages, which was suppressed by MLKL KO. Moreover, increased PTEN-induced kinase 1 (PINK1)-mediated mitophagy contributed to reduced oxidative DNA damage in hepatocytes and subsequent decreased activation of STING signaling in macrophages in MLKL KO mice. Our findings demonstrated a non-canonical role of MLKL in the pathogenesis of liver IR. MLKL deficiency significantly promoted PINK1-mediated mitophagy activation to inhibit oxidative DNA damage in hepatocytes, which in turn suppressed macrophage cGAS-STING activation and inflammatory liver IR injury.
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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.