ArticleNature metabolism2022
Citraconate inhibits ACOD1 (IRG1) catalysis, reduces interferon responses and oxidative stress, and modulates inflammation and cell metabolism.
Article in Nature metabolism, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 96 papers.
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96 citing papers in PubMed, 151 citations in OpenAlex.
- Robust structural, kinetic and biophysical characterization of wild-type human ACOD1, selected mutants and their interaction with citraconate.Journal of structural biology: X · 2026Article
- Itaconation and Succination as Metabolite-Derived Cysteine Modifications in Inflammatory Signalling: Biochemical Mechanisms, Chemoproteomic Mapping, and Therapeutic Opportunities.Cell biochemistry and biophysics · 2026Review
- Itaconate and its derivatives in human health and diseases.Signal transduction and targeted therapy · 2026Review
- Starter-Culture-Dependent Effects ofFoods (Basel, Switzerland) · 2026Article
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- Metabolic Bottlenecks and Opportunities: Reshaping the Tumor Microenvironment for Cancer Immunotherapy.Cells · 2026Review
- Inflammation in atherosclerosis: Drivers, mechanisms and therapies.Acta pharmaceutica Sinica. B · 2026Review
- Itaconate as a paracrine brake on thermogenesis.Nature metabolism · 2026Article
- Macrophage-to-myofibroblast transition-derived itaconate promotes bone metastasis in lung cancer through targeting of HSPA8.Experimental & molecular medicine · 2026Article
- Offense and defense: itaconate mediates bidirectional immune regulation of host-bacteria interaction.Journal of biomedical science · 2026Review
- Liquid Biopsy-Based Metabolomics in Epithelial Ovarian Cancer: Challenges, Methodological Advances and Translational Considerations.Diagnostics (Basel, Switzerland) · 2026Review
- Connexin Regulation and Modulation of Neural Stem Cell Differentiation Induced by Cell-Permeable Itaconate.Journal of cellular physiology · 2026Article
- KSR2 functions as a metabolic checkpoint for anti-PD-1 resistance by reprogramming glucose metabolism.Cancer immunology, immunotherapy : CII · 2026Article
- STAT1 itaconation prevents macrophage cytolistic mtDNA -induced inflammation in wear particle-induced aseptic loosening.Cell communication and signaling : CCS · 2026Article
- Human pneumovirus induces IFN-dependent expression of the immune-responsive gene 1 and is inhibited by 4-octyl itaconate in human macrophages.NAR molecular medicine · 2026Article
- Article
- Integrated metabolomic and microbiota analysis of semen: seasonal and morphological associations.Asian journal of andrology · 2026Article
- Mesaconate Alleviates Myocardial Ischemia/Reperfusion Injury and Cardiovascular Aging by Targeting GPR35 to Arrest Macrophage Inflammation.Inflammation · 2026Article
- ACOD1 expression in patients with sepsis: an exploratory study of associations with disease severity and immune signatures.BMC infectious diseases · 2026Article
- NRF2 activators and the inhibitor of nuclear export, selinexor, restrict coronaviruses by targeting a network involving ACE2, TMPRSS2, and XPO1 through an NRF2-independent mechanism.Communications biology · 2026Article
36 more citing papers are in PubMed but not listed here.
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22 authors at 7 institutions in 4 countries.
Funding
Abstract
Although the immunomodulatory and cytoprotective properties of itaconate have been studied extensively, it is not known whether its naturally occurring isomers mesaconate and citraconate have similar properties. Here, we show that itaconate is partially converted to mesaconate intracellularly and that mesaconate accumulation in macrophage activation depends on prior itaconate synthesis. When added to human cells in supraphysiological concentrations, all three isomers reduce lactate levels, whereas itaconate is the strongest succinate dehydrogenase (SDH) inhibitor. In cells infected with influenza A virus (IAV), all three isomers profoundly alter amino acid metabolism, modulate cytokine/chemokine release and reduce interferon signalling, oxidative stress and the release of viral particles. Of the three isomers, citraconate is the strongest electrophile and nuclear factor-erythroid 2-related factor 2 (NRF2) agonist. Only citraconate inhibits catalysis of itaconate by cis-aconitate decarboxylase (ACOD1), probably by competitive binding to the substrate-binding site. These results reveal mesaconate and citraconate as immunomodulatory, anti-oxidative and antiviral compounds, and citraconate as the first naturally occurring ACOD1 inhibitor.
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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.