Evolutionary conservation analysis reveals a primordial function of STING as a regulator of lipid metabolism via FADS2
Abstract The stimulator of interferon genes (STING) is a pivotal regulator of type I interferon (IFN) responses. Although the IFN system is confined to vertebrates, STING is present across metazoans and in some unicellular eukaryotes, suggesting involvement in distinct functions prior to vertebrate divergence. Here we explore the conservation of STING-mediated regulation of polyunsaturated fatty acid (PUFA) metabolism. We find that STING homologs from vertebrates, invertebrates, and unicellular eukaryotes interact with fatty acid desaturase 2 (FADS2), the rate-limiting enzyme in PUFA metabolism, and influence subsequent functional outputs. Specifically, we show that STING homologs differentially shape cell susceptibility to infection by DNA and RNA viruses independently of the activation of IFN responses, suggesting that STING-mediated metabolic pathway regulation may participate in primitive host defense mechanisms. Thus, we identify STING-mediated metabolic regulation as an evolutionarily conserved feature and a primordial function of STING.
Authors
- Nadine Laguette (ORCID: https://orcid.org/0000-0001-8072-5607)
- Niyazi Acar (ORCID: https://orcid.org/0000-0002-3401-8079)
- Adeline Augereau (ORCID: https://orcid.org/0000-0003-4165-7802)
- Soumyabrata Guha (ORCID: https://orcid.org/0000-0002-8996-6340)
- Pierre Boudinot (ORCID: https://orcid.org/0000-0002-7490-9677)
- Isabelle K. Vila (ORCID: https://orcid.org/0000-0002-6834-5721)
- Hanane Chamma (ORCID: https://orcid.org/0000-0003-2237-7741)
- Arielle Woznica (ORCID: https://orcid.org/0000-0002-3920-1737)
- Joanna Re
- Victoria Bergas
- Jean-Paul Paı̈s de Barros (ORCID: https://orcid.org/0000-0002-5124-2283)
- Morgane Chemarin
- Jennifer Barrat
- Yasmine Messaoud-Nacer
- Pierre Le Hars
- Collin McNairy
- Jenny Nguyen
- Stéphane Grégoire
Institutions
- Centre National de la Recherche Scientifique (FR)
- Inserm (FR)
- Université de Bourgogne (FR)
- Université de Versailles Saint-Quentin-en-Yvelines (FR)
- Université Paris-Saclay (FR)
- Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement (FR)
- Institut de Génétique Moléculaire de Montpellier (FR)
- Virologie et Immunologie Moléculaires (FR)
- Institut Agro Dijon (FR)
- Institut de Biologie Moléculaire et Cellulaire (FR)
- Université de Strasbourg (FR)
- The University of Texas at Austin (US)
Publication Details
- Journal
- Nature Communications
- Published
- 2026-08-14
- DOI
- https://doi.org/10.1038/s41467-026-76833-5
- Primary Topic
- interferon and immune responses
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Styrelsen för Internationellt Utvecklingssamarbete
- European Commission
- Agence Nationale de la Recherche
- Fondation pour la Recherche Médicale
- Agence Nationale de Recherches sur le Sida et les Hépatites Virales
- Fondation ARC pour la Recherche sur le Cancer
- Université de Montpellier
- Laboratoire d'Excellence EpiGenMed
- Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement
- Horizon 2020 Framework Programme