{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T16:45:09Z","timestamp":1788885909626,"version":"build-2803163510"},"reference-count":47,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T00:00:00Z","timestamp":1769731200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Major Program of National Natural Science Foundation of China","award":["82293651"],"award-info":[{"award-number":["82293651"]}]},{"name":"Key Projects of the National Natural Science Foundation of China","award":["82130055"],"award-info":[{"award-number":["82130055"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Alterations in mitochondrial fusion and fission dynamics are critical determinants of cellular fate. However, how stress-induced mitochondrial fusion and fission affect the physiological and pathological processes in cardiomyocytes remains poorly understood. Based on an established in vitro model of stress-induced cardiomyocyte injury using isoproterenol-treated H9c2 cells, this study aimed to investigate whether the dysregulation of mitochondrial dynamics\u2014specifically, an imbalance between fusion and fission\u2014activates the IRE1\u03b1-ASK1-JNK endoplasmic reticulum stress signaling pathway, thereby contributing to cardiomyocyte damage. Under this experimental paradigm, cell viability was evaluated using the CCK-8 assay. Concurrently, immunofluorescence staining was employed to assess reactive oxygen species accumulation, the expression of key mitochondrial fusion\/fission proteins, and components of the ER stress pathway (IRE1\u03b1, ASK1, and JNK). Results demonstrated that isoproterenol treatment elevated intracellular ROS levels and induced significant changes in both mitochondrial dynamics-related proteins and the IRE1\u03b1-ASK1-JNK signaling axis. In contrast, administration of the mitochondrial fission inhibitor Mdivi-1 attenuated ROS accumulation, restored the expression of the affected proteins toward normal levels, and alleviated cardiomyocyte injury. Collectively, these findings indicate that the disruption of mitochondrial fusion\/fission dynamics triggers endoplasmic reticulum stress via the IRE1\u03b1-ASK1-JNK cascade, which participates in the pathological progression of cardiomyocyte injury.<\/jats:p>","DOI":"10.3390\/ijms27031390","type":"journal-article","created":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T13:04:46Z","timestamp":1769778286000},"page":"1390","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Endoplasmic Reticulum Stress Induced by Turbulence of Mitochondrial Fusion and Fission Was Involved in Isoproterenol-Induced H9c2 Cell Injury"],"prefix":"10.3390","volume":"27","author":[{"given":"Shengnan","family":"Zhang","sequence":"first","affiliation":[{"name":"College of Basic Medical Science, Inner Mongolia Medical University, Hohhot 010059, China"},{"name":"Hebei Key Laboratory of Forensic Medicine, Collaborative Innovation Center of Forensic Medical Molecular Identification, Department of Forensic Medicine, Hebei Medical University, Shijiazhuang 050017, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liqin","family":"Chen","sequence":"additional","affiliation":[{"name":"College of Basic Medical Science, Inner Mongolia Medical University, Hohhot 010059, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuquan","family":"Jia","sequence":"additional","affiliation":[{"name":"College of Basic Medical Science, Inner Mongolia Medical University, Hohhot 010059, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuguang","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Basic Medical Science, Inner Mongolia Medical University, Hohhot 010059, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huimin","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Basic Medical Science, Inner Mongolia Medical University, Hohhot 010059, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9601-3188","authenticated-orcid":false,"given":"Weibo","family":"Shi","sequence":"additional","affiliation":[{"name":"Hebei Key Laboratory of Forensic Medicine, Collaborative Innovation Center of Forensic Medical Molecular Identification, Department of Forensic Medicine, Hebei Medical University, Shijiazhuang 050017, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Cong","sequence":"additional","affiliation":[{"name":"Hebei Key Laboratory of Forensic Medicine, Collaborative Innovation Center of Forensic Medical Molecular Identification, Department of Forensic Medicine, Hebei Medical University, Shijiazhuang 050017, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1146\/annurev-publhealth-031912-114452","article-title":"Stress and cardiovascular disease: An update on current knowledge","volume":"34","author":"Steptoe","year":"2013","journal-title":"Annu. 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