| First Author | O'Carroll SM | Year | 2024 |
| Journal | Nat Metab | PubMed ID | 39406969 |
| Mgi Jnum | J:357725 | Mgi Id | MGI:7764602 |
| Doi | 10.1038/s42255-024-01145-1 | Citation | O'Carroll SM, et al. (2024) Itaconate drives mtRNA-mediated type I interferon production through inhibition of succinate dehydrogenase. Nat Metab |
| abstractText | 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 IFNbeta 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. |
