Evidence map›Paper›PMID 39406969›Full record

ArticleNature metabolism2024

Itaconate drives mtRNA-mediated type I interferon production through inhibition of succinate dehydrogenase.

Shane M O'Carroll, Christian G Peace, Juliana E Toller-Kawahisa, Yukun Min, Alexander Hooftman, Sara Charki, Louise Kehoe, Maureen J O'Sullivan, Aline Zoller, Anne F Mcgettrick and 6 more

Erratum issuedAbstract read
In one paragraph

Article in Nature metabolism, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

31 citing papers in PubMed.

  1. Review
  2. Review
  3. Itaconate metabolism in regulated cell death.Molecular and cellular biochemistry · 2026
    Review
  4. Review
  5. Microparticles synthesized from itaconate polyesters enable metabolite delivery and elicit immunoregulatory outcomes.Journal of controlled release : official journal of the Controlled Release Society · 2026
    Article
  6. Article
  7. Itaconate alleviates LPS-induced septic liver injury by regulating ROS-PAD4-mediated macrophages extracellular traps through Nrf2.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026
    Article
  8. Article
  9. Palmitic Acid Promotes Antiviral Innate Immunity via ZDHHC20-Mediated CMPK2 Palmitoylation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  10. Article
  11. Role of itaconate in intestinal disease (Review).International journal of molecular medicine · 2026
    Review
  12. Article
  13. Article
  14. Itaconate modifications: Mechanisms and applications.Journal of intensive medicine · 2026
    Review
  15. Article
  16. Review
  17. Review
  18. Review
  19. Article
  20. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors.

Shane M O'Carroll *School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.ORCID http://orcid.org/0000-0002-3485-6128
Christian G Peace *School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.
Juliana E Toller-KawahisaSchool of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.
Yukun MinSchool of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.ORCID http://orcid.org/0009-0004-4771-6839
Alexander HooftmanSchool of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.ORCID http://orcid.org/0000-0002-5412-4012
Sara CharkiSchool of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.ORCID http://orcid.org/0009-0007-5825-5267
Louise KehoeHistology Lab, Children's Health Ireland at Crumlin, Dublin, Ireland.
Maureen J O'SullivanHistology Lab, Children's Health Ireland at Crumlin, Dublin, Ireland.
Aline ZollerSchool of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.
Anne F McgettrickSchool of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.ORCID http://orcid.org/0000-0001-6887-7229
Alessia ZottaSchool of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.
Emily A DaySchool of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.ORCID http://orcid.org/0000-0003-3245-5715
Maria SimarroDepartment of Cell Biology, Genetics, Histology and Pharmacology, Faculty of Medicine, University of Valladolid, Valladolid, Spain.ORCID http://orcid.org/0000-0001-8917-7328
Neali ArmstrongDepartment of Medicine, Division of Endocrinology, Stanford School of Medicine, Stanford, CA, USA.ORCID http://orcid.org/0009-0003-8775-7355
Justin P AnnesDepartment of Medicine, Division of Endocrinology, Stanford School of Medicine, Stanford, CA, USA.ORCID http://orcid.org/0000-0001-8431-3589
Luke A J O'NeillSchool of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland. laoneill@tcd.ie.ORCID http://orcid.org/0000-0002-4333-2748

Funding

The Role of Adenosine Kinase in Controlling Beta-Cell RegenerationR01DK101530 · NIDDK · STANFORD UNIVERSITY · PI ANNES, JUSTIN PIERCE · 2015 to 2024
$3.8M
Development of Beta-Cell-Targeted Regenerative Therapeutics Using A Novel Prodrug StrategyR01DK119955 · NIDDK · STANFORD UNIVERSITY · PI ANNES, JUSTIN PIERCE · 2019 to 2023
$2.1M
Developing A Platform Technology For β-Cell-Targeted Drug DeliveryU01DK136965 · NIDDK · STANFORD UNIVERSITY · PI Justin Pierce Annes · 2023 to 2026
$2.0M
EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council) 834370NIDDK NIH HHS R01 DK101530NIDDK NIH HHS R01 DK119955NIDDK NIH HHS U01 DK136965Science Foundation Ireland (SFI) 20/SPP/3685
6 · The paper itself

Abstract

Itaconate is one of the most highly upregulated metabolites in inflammatory macrophages and has been shown to have immunomodulatory properties. Here, we show that itaconate promotes type I interferon production through inhibition of succinate dehydrogenase (SDH). Using pharmacological and genetic approaches, we show that SDH inhibition by endogenous or exogenous itaconate leads to double-stranded mitochondrial RNA (mtRNA) release, which is dependent on the mitochondrial pore formed by VDAC1. In addition, the double-stranded RNA sensors MDA5 and RIG-I are required for IFNβ production in response to SDH inhibition by itaconate. Collectively, our data indicate that inhibition of SDH by itaconate links TCA cycle modulation to type I interferon production through mtRNA release.

Indexed as

Interferon Type IRNA, MitochondrialSuccinate DehydrogenaseSuccinatesAnimalsCitric Acid CycleDEAD Box Protein 58HumansInterferon-Induced Helicase, IFIH1MacrophagesMiceMitochondriaReceptors, ImmunologicRNA, Double-StrandedVoltage-Dependent Anion Channel 1DEAD Box Protein 58IFIH1 protein, humanInterferon-Induced Helicase, IFIH1Interferon Type Iitaconic acidReceptors, ImmunologicRIGI protein, humanRNA, Double-StrandedRNA, MitochondrialSuccinate DehydrogenaseSuccinatesVDAC1 protein, humanVoltage-Dependent Anion Channel 1

Identifiers

PMID39406969
PMCPMC12164541

What OpenQuestion holds

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Read underepoch 390

Registered trials

None linked

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.