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Sulfide quinone oxidoreductase (<jats:italic>SQOR<\/jats:italic>), located in the inner mitochondria membrane, is a crucial enzyme in sulfide metabolism. Here, we observed that <jats:italic>SQOR<\/jats:italic> was downregulated during colitis. Intestinal epithelial cells specific knockout of <jats:italic>SQOR<\/jats:italic> (<jats:italic>Sqor<\/jats:italic><jats:sup>CKO<\/jats:sup>) mice were more susceptible to acute ulcerative colitis (UC) with lower hydrogen sulfide (H<jats:sub>2<\/jats:sub>S) levels, and the absence of <jats:italic>SQOR<\/jats:italic> caused a breakdown of the epithelial barrier through disruption of the tight junction proteins. Furthermore, analysis of the mitochondrial morphology and functions revealed increased mitochondrial damage when <jats:italic>SQOR<\/jats:italic> deficiency. Mechanistically, it is observed that <jats:italic>SQOR<\/jats:italic> knockout increased lipid peroxidation, malondialdehyde (MDA) levels and ferroptosis. Further results demonstrated that <jats:italic>SQOR<\/jats:italic> may rely on inhibiting excessive mitochondrial division and promoting mitochondrial biogenesis to regulate reaction oxygen species (ROS) levels in intestinal epithelial cells. Treatment with ROS scavengers (NAC) showed significant reduced colonic inflammation symptoms observed in DSS\u2010treated <jats:italic>Sqor<\/jats:italic><jats:sup>CKO<\/jats:sup> mice. Collectively, these findings demonstrate the protective role of <jats:italic>SQOR<\/jats:italic> in intestinal epithelial cells in maintaining mitochondrial homeostasis by regulating ROS and providing novel insight into UC.<\/jats:p>","DOI":"10.1002\/mco2.70285","type":"journal-article","created":{"date-parts":[[2025,7,14]],"date-time":"2025-07-14T04:50:13Z","timestamp":1752468613000},"source":"Crossref","is-referenced-by-count":6,"title":["Sulfide Quinone Oxidoreductase Alleviates Acute Ulcerative Colitis by Regulating Mitochondrial Dysfunction"],"prefix":"10.1002","volume":"6","author":[{"given":"Hailin","family":"Ma","sequence":"first","affiliation":[{"name":"The State Key Laboratory of Pharmaceutical Biotechnology, College of Life Sciences Nanjing University  Nanjing PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuilian","family":"Fu","sequence":"additional","affiliation":[{"name":"The State Key Laboratory of Pharmaceutical Biotechnology, College of Life Sciences Nanjing University  Nanjing PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chujun","family":"Huang","sequence":"additional","affiliation":[{"name":"The State Key Laboratory of Pharmaceutical Biotechnology, College of Life Sciences Nanjing University  Nanjing PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Han","sequence":"additional","affiliation":[{"name":"The State Key Laboratory of Pharmaceutical Biotechnology, College of Life Sciences Nanjing University  Nanjing PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangfang","family":"Cai","sequence":"additional","affiliation":[{"name":"The State Key Laboratory of Pharmaceutical Biotechnology, College of Life Sciences Nanjing University  Nanjing PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dangran","family":"Li","sequence":"additional","affiliation":[{"name":"The State Key Laboratory of Pharmaceutical Biotechnology, College of Life Sciences Nanjing University  Nanjing PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Cheng","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory of Neuropsychiatric Diseases &amp; Institute of Neuroscience Soochow University  Suzhou PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongqin","family":"Zhuang","sequence":"additional","affiliation":[{"name":"The State Key Laboratory of Pharmaceutical Biotechnology, College of Life Sciences Nanjing University  Nanjing PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zi\u2010Chun","family":"Hua","sequence":"additional","affiliation":[{"name":"The State Key Laboratory of Pharmaceutical Biotechnology, College of Life Sciences Nanjing University  Nanjing PR China"},{"name":"Changzhou High\u2010Tech Research Institute of Nanjing University and Jiangsu Target Pharma Laboratories Inc.  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