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However, the mechanisms underlying cisplatin\u2010induced SGNs damage and subsequent SNHL are still under debate and there is no currently effective clinical treatment. Here, this study demonstrates that ferroptosis is triggered in SGNs following exposure to cisplatin. Inhibiting ferroptosis protects against cisplatin\u2010induced SGNs damage and hearing loss, while inducing ferroptosis intensifies these effects. Furthermore, cisplatin prompts nuclear receptor coactivator 4 (NCOA4)\u2010mediated ferritinophagy in SGNs, while knocking down NCOA4 mitigates cisplatin\u2010induced ferroptosis and hearing loss. Notably, the upstream regulator of NCOA4 is identified and transcription factor forkhead box O1 (FOXO1) is shown to directly suppress NCOA4 expression in SGNs. The knocking down of FOXO1 amplifies NCOA4\u2010mediated ferritinophagy, increases ferroptosis and lipid peroxidation, while disrupting the interaction between FOXO1 and NCOA4 in NCOA4 knock out mice prevents the cisplatin\u2010induced SGN ferroptosis and hearing loss. Collectively, this study highlights the critical role of the FOXO1\u2010NCOA4 axis in regulating ferritinophagy and ferroptosis in cisplatin\u2010induced SGNs damage, offering promising therapeutic targets for SNHL mitigation.<\/jats:p>","DOI":"10.1002\/advs.202402671","type":"journal-article","created":{"date-parts":[[2024,8,29]],"date-time":"2024-08-29T06:25:03Z","timestamp":1724912703000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["FOXO1\u2010NCOA4 Axis Contributes to Cisplatin\u2010Induced Cochlea Spiral Ganglion Neuron Ferroptosis via Ferritinophagy"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-0621-2851","authenticated-orcid":false,"given":"Xue","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Otolaryngology\u2010Head and Neck Surgery Shandong Provincial ENT Hospital Shandong University  Jinan 250022 China"},{"name":"Shandong Institute of 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Institute of Otorhinolaryngology  Jinan 250022 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinzhu","family":"Zhuang","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2010Head and Neck Surgery Shandong Provincial ENT Hospital Shandong University  Jinan 250022 China"},{"name":"Shandong Institute of Otorhinolaryngology  Jinan 250022 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Man","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2010Head and Neck Surgery Shandong Provincial ENT Hospital Shandong University  Jinan 250022 China"},{"name":"Shandong Institute of Otorhinolaryngology  Jinan 250022 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weibin","family":"An","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2010Head and Neck Surgery Shandong Provincial ENT Hospital Shandong University  Jinan 250022 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