ArticleThe Journal of biological chemistry2016
Immunoresponsive Gene 1 and Itaconate Inhibit Succinate Dehydrogenase to Modulate Intracellular Succinate Levels.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 326 papers.
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Who cites it
326 citing papers in PubMed, 502 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
- Microparticles synthesized from itaconate polyesters enable metabolite delivery and elicit immunoregulatory outcomes.Journal of controlled release : official journal of the Controlled Release Society · 2026Article
- Metabolomics of in vivo inflammation identifies soluble sialic acid as a conserved myeloid-cell metabolite.The Journal of biological chemistry · 2026Article
- Itaconate and its derivatives in human health and diseases.Signal transduction and targeted therapy · 2026Review
- Article
- Macrophage-derived itaconate is a negative regulator of adipose tissue thermogenesis.Nature metabolism · 2026Article
- Metabolite and nutrient regulation of macrophages in obesity and metabolic disease.Nature reviews. Immunology · 2026Review
- Metabolomics ofbioRxiv : the preprint server for biology · 2026Article
- Review
- Identification of a metabolic-immune crosstalk in Still's disease: monocyte/macrophage-derived immunometabolite itaconate dictates hepatic immunopathology via the CXCL10-CD8 T cell axis.Experimental & molecular medicine · 2026Article
- The alkylation of AIM2 by itaconate mediates macrophage PANoptosis during sepsis.Cellular & molecular immunology · 2026Article
- Metabolic pattern changes of macrophages during cancer development and progression.Journal of translational medicine · 2026Review
- Article
- STAT1 itaconation prevents macrophage cytolistic mtDNA -induced inflammation in wear particle-induced aseptic loosening.Cell communication and signaling : CCS · 2026Article
- iNOS modulates inflammatory responses in an NO-independent manner through direct interaction with IRG1 in mitochondria.Nature metabolism · 2026Article
- Article
- Discovery of metabolites produced by reactions between central carbon metabolites and cysteine that mark inflammatory macrophages.bioRxiv : the preprint server for biology · 2026Article
- ACOD1 expression in patients with sepsis: an exploratory study of associations with disease severity and immune signatures.BMC infectious diseases · 2026Article
- Nutrients and Metabolites as Signalling Molecules in Osteoclasts.Current osteoporosis reports · 2026Review
- A proteomics and redox proteomics approach to understanding ARDS heterogeneity.Scientific reports · 2026Article
266 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
Abstract
Metabolic reprogramming is emerging as a hallmark of the innate immune response, and the dynamic control of metabolites such as succinate serves to facilitate the execution of inflammatory responses in macrophages and other immune cells. Immunoresponsive gene 1 (Irg1) expression is induced by inflammatory stimuli, and its enzyme product cis-aconitate decarboxylase catalyzes the production of itaconate from the tricarboxylic acid cycle. Here we identify an immunometabolic regulatory pathway that links Irg1 and itaconate production to the succinate accumulation that occurs in the context of innate immune responses. Itaconate levels and Irg1 expression correlate strongly with succinate during LPS exposure in macrophages and non-immune cells. We demonstrate that itaconate acts as an endogenous succinate dehydrogenase inhibitor to cause succinate accumulation. Loss of itaconate production in activated macrophages from Irg1(-/-) mice decreases the accumulation of succinate in response to LPS exposure. This metabolic network links the innate immune response and tricarboxylic acid metabolism to function of the electron transport chain.
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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.