ArticleCell reports2023
Pyruvate dehydrogenase kinase supports macrophage NLRP3 inflammasome activation during acute inflammation.
Article in Cell reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 46 citations in OpenAlex.
- The role of cellular senescence in sepsis and its mechanism in copper death: An analysis based on machine learning.Medicine · 2026Article
- Advances in the mechanisms of the NLRP3 inflammasome in sepsis‑induced cardiomyopathy and targeted therapeutic studies (Review).Molecular medicine reports · 2026Review
- Regulatory Mechanisms and Safety Evaluation of Exogenous Progesterone for Suppression of Rutting Behavior in Male Sika Deer (Animals : an open access journal from MDPI · 2026Article
- Article
- The regulatory mechanism of NLRP3 inflammasome in the "immune paralytic-overactivation" imbalance in sepsis: the latest progress from molecular signaling to clinical translation.Frontiers in immunology · 2026Review
- Bidirectional Regulation of NLRP3 Inflammasome and Mitochondrial Quality Control in Sepsis: Mechanisms and Therapeutic Implications.Mediators of inflammation · 2026Review
- Macrophage Hypoxia Signaling Pathways and Their Roles in Sepsis.Journal of inflammation research · 2026Review
- Crosstalk of mitochondrial dysfunction and macrophage polarization in sepsis.Frontiers in immunology · 2026Review
- NLRP3 inflammasome expression in pediatric asthma: sputum-based insights, inflammatory mechanisms, and targeted therapeutic strategies.Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology · 2025Review
- Mesencephalic Astrocyte-Derived Neurotrophic Factor Binds BAX to Preserve Mitochondrial Homeostasis and Energy Metabolism for Relieving Myocardial Hypertrophy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Sepsis-Related Cardiomyopathy: Advances in Diagnosis and Treatment.Reviews in cardiovascular medicine · 2025Review
- NIR Driven Pd/Cerium Oxide Nano-Heterojunction for Enhanced Salvaging Sepsis Induced Acute Liver Injury via Reprogramming Redox Homeostasis in Synergy with Inducing Autophagy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- NLRP3 Inflammasome-Mediated Pyroptosis in Osteoporosis: Osteoimmune Mechanisms and Therapeutic Targeting.Journal of cellular and molecular medicine · 2025Review
- miR-370-3p affects the progression of postmenopausal osteoporosis through targeting INO80.Hereditas · 2025Article
- Updated insights into the molecular networks for NLRP3 inflammasome activation.Cellular & molecular immunology · 2025Review
- Mechanical Force Triggers Macrophage Pyroptosis and Sterile Inflammation by Disrupting Cellular Energy Metabolism.International journal of molecular sciences · 2025Article
- A review on NLRP3 inflammasome modulation by animal venom proteins/peptides: mechanisms and therapeutic insights.Inflammopharmacology · 2025Review
- Mitochondrial dynamics at the intersection of macrophage polarization and metabolism.Frontiers in immunology · 2025Review
- Regulation of the NLRP3 inflammasome by autophagy and mitophagy.Immunological reviews · 2025Review
- Antroquinonol reduces IL-1β production in macrophages through enhancing the DNA methylation ofFrontiers in nutrition · 2025Article
Corrections and comments
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Authors and funding
18 authors at 4 institutions in 2 countries.
Funding
Abstract
Activating the macrophage NLRP3 inflammasome can promote excessive inflammation with severe cell and tissue damage and organ dysfunction. Here, we show that pharmacological or genetic inhibition of pyruvate dehydrogenase kinase (PDHK) significantly attenuates NLRP3 inflammasome activation in murine and human macrophages and septic mice by lowering caspase-1 cleavage and interleukin-1β (IL-1β) secretion. Inhibiting PDHK reverses NLRP3 inflammasome-induced metabolic reprogramming, enhances autophagy, promotes mitochondrial fusion over fission, preserves crista ultrastructure, and attenuates mitochondrial reactive oxygen species (ROS) production. The suppressive effect of PDHK inhibition on the NLRP3 inflammasome is independent of its canonical role as a pyruvate dehydrogenase regulator. Our study suggests a non-canonical role of mitochondrial PDHK in promoting mitochondrial stress and supporting NLRP3 inflammasome activation during acute inflammation.
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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.