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Bmi1 is a member of the Polycomb protein family and has been reported to regulate mitochondrial function and ROS level in thymocytes and neurons. In this study, we reported the expression of Bmi1 in mouse cochlea and investigated the role of Bmi1 in hair cell survival. Bmi1 expressed in hair cells and supporting cells in mouse cochlea. Bmi1<jats:sup>\u2212\/\u2212<\/jats:sup> mice displayed severe hearing loss and patched outer hair cell loss from postnatal day 22. Ototoxic drug-induced hair cells loss dramatically increased in Bmi1<jats:sup>\u2212\/\u2212<\/jats:sup> mice compared with that in wild-type controls both <jats:italic>in vivo<\/jats:italic> and <jats:italic>in vitro<\/jats:italic>, indicating Bmi1<jats:sup>\u2212\/\u2212<\/jats:sup> hair cells were significantly more sensitive to ototoxic drug-induced damage. Cleaved caspase-3 and TUNEL staining demonstrated that apoptosis was involved in the increased hair cell loss of Bmi1<jats:sup>\u2212\/\u2212<\/jats:sup> mice. Aminophenyl fluorescein and MitoSOX Red staining showed the level of free radicals and mitochondrial ROS increased in Bmi1<jats:sup>\u2212\/\u2212<\/jats:sup> hair cells due to the aggravated disequilibrium of antioxidant\u2013prooxidant balance. Furthermore, the antioxidant <jats:italic>N<\/jats:italic>-acetylcysteine rescued Bmi1<jats:sup>\u2212\/\u2212<\/jats:sup> hair cells from neomycin injury both <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic>, suggesting that ROS accumulation was mainly responsible for the increased aminoglycosides sensitivity in Bmi1<jats:sup>\u2212\/\u2212<\/jats:sup> hair cells. Our findings demonstrate that Bmi1 has an important role in hair cell survival by controlling redox balance and ROS level, thus suggesting that Bmi1 may work as a new therapeutic target for the prevention of hair cell death.<\/jats:p>","DOI":"10.1038\/cddis.2014.549","type":"journal-article","created":{"date-parts":[[2015,1,22]],"date-time":"2015-01-22T13:50:49Z","timestamp":1421934649000},"page":"e1605-e1605","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["Bmi1 regulates auditory hair cell survival by maintaining redox balance"],"prefix":"10.1038","volume":"6","author":[{"given":"Y","family":"Chen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3394-2278","authenticated-orcid":false,"given":"L","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"W","family":"Ni","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Y","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S","family":"Sun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D","family":"Miao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R","family":"Chai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2015,1,22]]},"reference":[{"key":"BFcddis2014549_CR1","doi-asserted-by":"crossref","first-page":"3935","DOI":"10.1242\/dev.125.20.3935","volume":"125","author":"M Xiang","year":"1998","unstructured":"Xiang M, Gao WQ, Hasson T, Shin JJ . 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