ArticleJCI insight2018
Pyruvate dehydrogenase complex stimulation promotes immunometabolic homeostasis and sepsis survival.
Article in JCI insight, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 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.
The trial behind it
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Who cites it
42 citing papers in PubMed, 66 citations in OpenAlex.
- Extension of lifespan by epicatechin, halofuginone and mitoglitazone in male but not female genetically heterogeneous mice.GeroScience · 2026Article
- Sepsis and the immunometabolic inflammatory response.npj metabolic health and disease · 2026Review
- Elevated plasma cholesterol improves sepsis outcome by promoting hepatic metabolic reprogramming.Frontiers in immunology · 2026Article
- Pyruvate Dehydrogenase Complex Stimulation With Dichloroacetate May Improve Septic Cardiac Dysfunction.Shock (Augusta, Ga.) · 2025Article
- Mechanisms of immune suppression in sepsis/shock: one investigator's/lab group's experience (SLB 2024 legacy award presentation).Journal of leukocyte biology · 2025Article
- Myocardial pyruvate dehydrogenase kinase 4 drives sex-specific cardiac responses to endotoxemia.JCI insight · 2025Article
- Mitochondria at the Heart of Sepsis: Mechanisms, Metabolism, and Sex Differences.International journal of molecular sciences · 2025Review
- Sepsis-induced changes in pyruvate metabolism: insights and potential therapeutic approaches.EMBO molecular medicine · 2024Review
- Metabolic specialization drives reduced pathogenicity in Pseudomonas aeruginosa isolates from cystic fibrosis patients.PLoS biology · 2024Article
- The Values of PDK1 and LDH Levels in Patients with Sepsis and Septic Shock: A Prospective Observational Study.Journal of inflammation research · 2024Article
- Article
- Preclinical Study in Mouse Thymus and Thymocytes: Effects of Treatment with a Combination of Sodium Dichloroacetate and Sodium Valproate on Infectious Inflammation Pathways.Pharmaceutics · 2023Article
- Regulating mitochondrial metabolism by targeting pyruvate dehydrogenase with dichloroacetate, a metabolic messenger.Biochimica et biophysica acta. Molecular basis of disease · 2023Review
- Glutathionylation of pyruvate dehydrogenase complex E2 and inflammatory cytokine production during acute inflammation are magnified by mitochondrial oxidative stress.Redox biology · 2023Article
- Early hyperlipidemia triggers metabolomic reprogramming with increased SAH, increased acetyl-CoA-cholesterol synthesis, and decreased glycolysis.Redox biology · 2023Article
- Pyruvate dehydrogenase kinase regulates vascular inflammation in atherosclerosis and increases cardiovascular risk.Cardiovascular research · 2023Article
- Proteomics as a Tool for the Study of Mitochondrial Proteome, Its Dysfunctionality and Pathological Consequences in Cardiovascular Diseases.International journal of molecular sciences · 2023Review
- Pyruvate dehydrogenase kinase supports macrophage NLRP3 inflammasome activation during acute inflammation.Cell reports · 2023Article
- Pyruvate dehydrogenase kinase regulates macrophage polarization in metabolic and inflammatory diseases.Frontiers in immunology · 2023Review
- Sepsis, pyruvate, and mitochondria energy supply chain shortage.Journal of leukocyte biology · 2022Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
Limited understanding of the mechanisms responsible for life-threatening organ and immune failure hampers scientists' ability to design sepsis treatments. Pyruvate dehydrogenase kinase 1 (PDK1) is persistently expressed in immune-tolerant monocytes of septic mice and humans and deactivates mitochondrial pyruvate dehydrogenase complex (PDC), the gate-keeping enzyme for glucose oxidation. Here, we show that targeting PDK with its prototypic inhibitor dichloroacetate (DCA) reactivates PDC; increases mitochondrial oxidative bioenergetics in isolated hepatocytes and splenocytes; promotes vascular, immune, and organ homeostasis; accelerates bacterial clearance; and increases survival. These results indicate that the PDC/PDK axis is a druggable mitochondrial target for promoting immunometabolic and organ homeostasis during sepsis.
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What OpenQuestion holds
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.