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However, the role of the Nrf2\/PHB2 pathway in SA\u2010induced ALI (SA\u2010ALI) remains unclear. In this study, serum samples were collected from SA\u2010sepsis patients, and a SA\u2010ALI mouse model was established by grouping WT and Nrf2<jats:sup>\u2212\/\u2212<\/jats:sup> mice after 6\u00a0h of intraperitoneal injection. A cell model simulating SA\u2010ALI was developed using lipoteichoic acid (LTA) treatment. The results showed reduced serum Nrf2 levels in SA\u2010sepsis patients, negatively correlated with the severity of ALI. In SA\u2010ALI mice, downregulation of Nrf2 impaired mitochondrial function and exacerbated inflammation\u2010induced ALI. Moreover, PHB2 translocation from mitochondria to the cytoplasm was observed in SA\u2010ALI. The p\u2010Nrf2\/total\u2010Nrf2 ratio increased in A549 cells with LTA concentration and treatment duration. Nrf2 overexpression in LTA\u2010treated A549 cells elevated PHB2 content on the inner mitochondrial membrane, preserving genomic integrity, reducing oxidative stress, and inhibiting excessive mitochondrial division. Bioinformatic analysis and dual\u2010luciferase reporter assay confirmed direct binding of Nrf2 to the PHB2 promoter, resulting in increased PHB2 expression. In conclusion, Nrf2 plays a role in alleviating SA\u2010ALI by directly regulating PHB2 transcription and maintaining mitochondrial function in lung cells.<\/jats:p>","DOI":"10.1002\/mco2.448","type":"journal-article","created":{"date-parts":[[2023,12,8]],"date-time":"2023-12-08T01:13:12Z","timestamp":1701997992000},"source":"Crossref","is-referenced-by-count":16,"title":["Nrf2\/PHB2 alleviates mitochondrial damage and protects against <i>Staphylococcus aureus<\/i>\u2010induced acute lung injury"],"prefix":"10.1002","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7056-2883","authenticated-orcid":false,"given":"Si\u2010Hao","family":"Jin","sequence":"first","affiliation":[{"name":"Department of Cardiothoracic Surgery Affiliated Hospital of Jiangnan University  Wuxi China"},{"name":"Department of Basic Medicine, Wuxi School of Medicine Jiangnan University Wuxi China"},{"name":"Department of Nursing, School of Medicine Shaoxing Vocational &amp; Technical College Shaoxing 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