{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T14:08:59Z","timestamp":1789135739547,"version":"build-2803163510"},"reference-count":60,"publisher":"American Chemical Society (ACS)","issue":"9","license":[{"start":{"date-parts":[[2026,8,8]],"date-time":"2026-08-08T00:00:00Z","timestamp":1786147200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,8,8]],"date-time":"2026-08-08T00:00:00Z","timestamp":1786147200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,8,8]],"date-time":"2026-08-08T00:00:00Z","timestamp":1786147200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Biochanin A (BCA) is a natural isoflavone found in chickpeas and soybeans. Although its biological activity is well established, the role of BCA in anti-infective immunity has not yet been fully elucidated. In this study, we demonstrated that BCA exploited the transcription factor ATFS-1 to trigger the mitochondrial unfolded protein response (UPRmt). In Caenorhabditis elegans (C. elegans), BCA increased resistance to Pseudomonas aeruginosa (P. aeruginosa PA14) and other pathogens in a dosage-dependent manner by reducing the intestinal bacterial load rather than directly inhibiting bacterial proliferation. By screening classical signaling pathways, we found that the BCA-mediated protective effect was entirely dependent on the atfs-1 gene, as BCA induced the nuclear translocation of ATFS-1 and upregulated UPRmt and immune effector factors. Notably, this mechanism was evolutionarily conserved. In a mouse model, BCA dose-dependently increased survival rates, reduced bacterial load in the lungs, and upregulated the expression of ATF5 (the mammalian homolog of ATFS-1) and mitochondrial chaperone proteins. This study is the first to reveal a cross-species conserved link between BCA, the mitochondrial stress response, and the host immune system, providing a promising therapeutic target for the management of clinical bacterial infections.<\/jats:p>","DOI":"10.1021\/acsinfecdis.6c00007","type":"journal-article","created":{"date-parts":[[2026,8,8]],"date-time":"2026-08-08T15:02:08Z","timestamp":1786201328000},"page":"3019-3027","source":"Crossref","is-referenced-by-count":0,"title":["Biochanin A\nActivates Mitochondrial UPR to Protect\nthe Host against Pathogenic Bacterial Infection through the Conserved\nTranscription Factor ATFS-1\/ATF5"],"prefix":"10.1021","volume":"12","author":[{"given":"Qiuyu","family":"Song","sequence":"first","affiliation":[{"name":"Zunyi Medical University , , , ,","place":["Zunyi, Guizhou, China, 563000"]},{"name":"Zunyi Medical University , , , ,","place":["Zunyi, Guizhou, China, 563000"]},{"name":"Zunyi Medical University , , , ,","place":["Zunyi, Guizhou, China, 563000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1603-8946","authenticated-orcid":true,"given":"Yi","family":"Xiao","sequence":"additional","affiliation":[{"name":"Zunyi Medical University , , , ,","place":["Zunyi, Guizhou, China, 563000"]},{"name":"Zunyi Medical University , , , ,","place":["Zunyi, Guizhou, China, 563000"]},{"name":"Zunyi Medical University , , , ,","place":["Zunyi, Guizhou, China, 563000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Xiao","sequence":"additional","affiliation":[{"name":"Zunyi Medical University , , , ,","place":["Zunyi, Guizhou, China, 563000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Liu","sequence":"additional","affiliation":[{"name":"Zunyi Medical University , , , ,","place":["Zunyi, Guizhou, China, 563000"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,8]]},"reference":[{"issue":"8","key":"2026091109093124500_cit1","doi-asserted-by":"publisher","first-page":"656","DOI":"10.1177\/1753425917732822","article-title":"PKA\/KIN-1 mediates\ninnate immune responses to bacterial pathogens in Caenorhabditis elegans","volume":"23","author":"Xiao","year":"2017","journal-title":"Innate Immun."},{"issue":"7285","key":"2026091109093124500_cit2","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1038\/nature08780","article-title":"Circulating\nmitochondrial DAMPs cause inflammatory responses to injury","volume":"464","author":"Zhang","year":"2010","journal-title":"Nature"},{"issue":"42","key":"2026091109093124500_cit3","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.142ec361","article-title":"Nematode\nImmune Defenses","volume":"1","author":"Kelner","year":"2008","journal-title":"Sci. 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