Viral infection activates the IRF1-BAK axis to drive mitochondria-derived inflammation.

Authors

Meidi Ye, Yifei Wang, Zhenqiong Guan, Zhenxing Zhou, Zihan Guan, Yulan Zhang, Shufen Li, Ke Peng

Published in

Cell reports. Volume 45. Issue 10. Pages 117968. Sep 16, 2026. Epub Sep 16, 2026.

Abstract

Mitochondria can drive the development of inflammatory pathogenesis through releasing pro-inflammatory DAMPs, a process often triggered during virus infection. Whether a common mechanism exists that promotes virus-triggered mitochondria-derived inflammation is currently unknown. Here, we report that BAK is an interferon-stimulated gene that is up-regulated by the STAT1-IRF1 axis during virus infection to induce mitochondria-derived inflammatory pathogenesis. Viral infection triggers STAT1-dependent up-regulation of IRF1, which binds to an identified ISRE site in the BAK-promoter, inducing BAK up-regulation. Up-regulated BAK accumulates in the mitochondria triggering mitochondrial outer-membrane permeabilization and inflammatory responses. Both RNA and DNA viruses trigger the IRF1-mediated BAK up-regulation and mitochondria-derived inflammation. Using the Bak^-/- mouse model, we showed that both IAV and SFTSV, two viruses that induce severe inflammation in patients, trigger BAK up-regulation and BAK-dependent lethal inflammation. These results reveal a common mechanism that drives mitochondria-derived pathogenic inflammation, which can be targeted for developing anti-inflammatory therapeutics.

PMID:
42747967
Bibliographic data and abstract were imported from PubMed on 17 Sep 2026.

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