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To elucidate the resistance mechanism, we compared transcriptomes of susceptible (XY-PS) and laboratory-selected resistant (XY-PR) strains. The mitochondrial cytochrome P450 gene CYP12A2 emerged as a key candidate. RT-qPCR confirmed CYP12A2 was upregulated approximately 8-fold in XY-PR and 9-fold in a field-collected resistant strain (ZL-PR). Furthermore, RNA interference (RNAi) targeting CYP12A2 significantly increased larval susceptibility to pyridalyl. Recombinant CYP12A2 expressed in Sf9 cells specifically metabolized pyridalyl, producing a distinct hydroxylated metabolite identified via UPLC-MS\/MS. These findings represent direct evidence of P450-mediated metabolic detoxification of pyridalyl. Ultimately, this unveils a novel biochemical adaptation in P. xylostella, establishing CYP12A2 as a critical biomarker for field resistance monitoring and a promising target for integrated insecticide resistance management (IRM) strategies.<\/jats:p>","DOI":"10.1021\/acs.jafc.6c09266","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T07:36:40Z","timestamp":1785137800000},"page":"23472-23480","source":"Crossref","is-referenced-by-count":1,"title":["Overexpression\nof Cytochrome P450\n                    <i>CYP12A2<\/i>\n                    Contributes to Pyridalyl\nResistance in\n                    <i>Plutella xylostella<\/i>"],"prefix":"10.1021","volume":"74","author":[{"given":"Falong","family":"Wang","sequence":"first","affiliation":[{"name":"Central China Normal University , , ,","place":["Wuhan, P. R. China, 430079"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunyan","family":"Yin","sequence":"additional","affiliation":[{"name":"Hubei Collaborative Innovation Center for Bioactive Polypeptide Diabetes Drugs , , ,","place":["Wuhan, P. R. China, 430223"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyuan","family":"Qin","sequence":"additional","affiliation":[{"name":"Central China Normal University , , ,","place":["Wuhan, P. R. China, 430079"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Awad","family":"Ateia","sequence":"additional","affiliation":[{"name":"Central China Normal University , , ,","place":["Wuhan, P. R. China, 430079"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4090-8411","authenticated-orcid":true,"given":"Gefei","family":"Hao","sequence":"additional","affiliation":[{"name":"Guizhou University , , ,","place":["Guiyang, P. R. China, 550025"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5933-9928","authenticated-orcid":true,"given":"Zhenyu","family":"Wang","sequence":"additional","affiliation":[{"name":"Central China Normal University , , ,","place":["Wuhan, P. R. China, 430079"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4384-2593","authenticated-orcid":true,"given":"Guangfu","family":"Yang","sequence":"additional","affiliation":[{"name":"Central China Normal University , , ,","place":["Wuhan, P. R. 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Physiol."},{"key":"2026080510095893700_cit17","first-page":"335","article-title":"Ultrastructural\neffects of pyridalyl, an insecticidal agent, on epidermal cells of\nSpodoptera litura larvae and cultured insect cells Sf9","volume":"6","author":"Meda","year":"2006","journal-title":"J. Insect Sci."},{"key":"2026080510095893700_cit18","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1016\/j.ibmb.2011.03.007","article-title":"The molecular\naction of the novel insecticide, pyridalyl","volume":"41","author":"Powell","year":"2011","journal-title":"Insect Biochem. Mol. Biol."},{"key":"2026080510095893700_cit19","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1093\/jee\/toy334","article-title":"Monitoring, cross-resistance,\ninheritance,\nand synergism of Plutella xylostella (Lepidoptera: Plutellidae) resistance to pyridalyl in China","volume":"112","author":"Yin","year":"2019","journal-title":"J. Econ. 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Insect Sci."}],"container-title":["Journal of Agricultural\nand Food Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acs.jafc.6c09266","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/jafcau\/article-pdf\/74\/30\/23472\/66269257\/acs.jafc.6c09266.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/jafcau\/article-pdf\/74\/30\/23472\/66269257\/acs.jafc.6c09266.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T14:20:43Z","timestamp":1785939643000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/jafcau\/article\/74\/30\/23472\/5233317\/Overexpression-of-Cytochrome-P450-CYP12A2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,26]]},"references-count":44,"journal-issue":{"issue":"30","published-online":{"date-parts":[[2026,7,26]]},"published-print":{"date-parts":[[2026,8,5]]}},"URL":"https:\/\/doi.org\/10.1021\/acs.jafc.6c09266","relation":{},"ISSN":["0021-8561","1520-5118"],"issn-type":[{"value":"0021-8561","type":"print"},{"value":"1520-5118","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,26]]}}}