{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T08:42:01Z","timestamp":1776328921833,"version":"3.50.1"},"reference-count":32,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2025,7,31]],"date-time":"2025-07-31T00:00:00Z","timestamp":1753920000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Gastro and Hepatol"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background and Aims<\/jats:title><jats:p>The role of mitochondrial dynamics in gastroesophageal reflux disease (GERD) remains unclear. We investigated how bile acid\u2010induced mitochondrial dysfunction triggers mucosal inflammation and explored therapeutic targets.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Esophageal mucosal biopsies from 12 GERD patients and 12 controls underwent RNA\u2010seq. Human esophageal epithelial cells (HEEC) were treated with acidic bile salts (ABS, pH\u20095.5). Mitochondrial morphology (TOMM20 immunofluorescence), function (TMRM\/MitoSOX staining), and DRP1 post\u2010translational modifications (non\u2010reducing Western blot) were analyzed. DRP1 knockdown (shRNA) and pharmacological inhibition (H\u201089) were used to validate mechanisms.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>RNA\u2010seq revealed enrichment of mitochondrial fission and NF\u2010\u03baB pathways in GERD patients. ABS exposure in HEEC increased DRP1 Ser637 phosphorylation, inducing mitochondrial fragmentation, membrane potential loss, and mtROS overproduction. Paradoxically, DRP1 knockdown exacerbated mitochondrial damage and amplified NF\u2010\u03baB activation. H\u201089 suppressed DRP1 Ser637 phosphorylation, restored mitochondrial function, and attenuated IL\u20106\/IL\u20108 secretion. This effect was abolished in DRP1\u2010knockdown cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>ABS\u2010induced DRP1 Ser637 phosphorylation drives mitochondrial fragmentation and mtROS\u2010dependent NF\u2010\u03baB activation in GERD. DRP1\u2010mediated fission paradoxically limits mucosal damage by enabling quality control. Targeting DRP1 phosphorylation may offer a novel therapeutic strategy to break the mitochondrial\u2010inflammation vicious cycle in GERD.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jgh.70056","type":"journal-article","created":{"date-parts":[[2025,7,31]],"date-time":"2025-07-31T11:24:43Z","timestamp":1753961083000},"page":"2507-2517","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Targeting DRP1Ser637 Phosphorylation Alleviates Acidic Bile Salt\u2010Induced NF\u2010\u03baB Activation via Mitochondrial Protection"],"prefix":"10.1111","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-9175-2137","authenticated-orcid":false,"given":"Yanqing","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Gastroenterology The First Affiliated Hospital With Nanjing Medical University  Nanjing Jiangsu 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