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To explore the effect of mitochondrial calcium uniporter (MCU) on mitochondrial dynamic imbalance under I\/R and its related signal pathways, a mouse myocardial I\/R model and hypoxia\/reoxygenation model of mouse cardiomyocytes were established. The expression of MCU during I\/R increased and related to myocardial injury, enhancement of mitochondrial fission, inhibition of mitochondrial fusion and mitophagy. Suppressing MCU functions by Ru360 during I\/R could reduce myocardial infarction area and cardiomyocyte apoptosis, alleviate mitochondrial fission and restore mitochondrial fusion and mitophagy. However, spermine administration, which could enhance MCU function, deteriorated the above\u2010mentioned myocardial cell injury and mitochondrial dynamic imbalanced. In addition, up\u2010regulation of MCU promoted the expression and activation of calpain\u20101\/2 and down\u2010regulated the expression of Optic atrophy type 1 (OPA1). Meantime, in transgenic mice (overexpression calpastatin, the endogenous inhibitor of calpain) I\/R model and OPA1 knock\u2010down cultured cell. In I\/R models of transgenic mice over\u2010expressing calpastatin, which is the endogenous inhibitor of calpain, and in H\/R models with siOPA1 transfection, inhibition of calpains could enhance mitochondrial fusion and mitophagy, and inhibit excessive mitochondrion fission and apoptosis through OPA1. Therefore, we conclude that during I\/R, MCU up\u2010regulation induces calpain activation, which down\u2010regulates OPA1, consequently leading to mitochondrial dynamic imbalance.<\/jats:p>","DOI":"10.1111\/jcmm.14662","type":"journal-article","created":{"date-parts":[[2019,9,9]],"date-time":"2019-09-09T20:09:45Z","timestamp":1568059785000},"page":"7830-7843","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":137,"title":["MCU Up\u2010regulation contributes to myocardial ischemia\u2010reperfusion Injury through calpain\/OPA\u20101\u2013mediated mitochondrial fusion\/mitophagy Inhibition"],"prefix":"10.1111","volume":"23","author":[{"given":"Lichun","family":"Guan","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Surgery Shanghai General Hospital, Shanghai Jiao Tong University, School of Medicine Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhimei","family":"Che","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Renji Hospital, Shanghai Jiao Tong University, School of Medicine Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangdong","family":"Meng","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery Shanghai General Hospital, Shanghai Jiao Tong University, School of Medicine Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Cardiology Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University Shanghai Shi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minghui","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Cardiology Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University Shanghai Shi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziqin","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Cardiology Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University Shanghai Shi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Cardiology Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University Shanghai Shi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dicheng","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery Shanghai General Hospital, Shanghai Jiao Tong University, School of Medicine Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0042-2196","authenticated-orcid":false,"given":"Min","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery Shanghai General Hospital, Shanghai Jiao Tong University, School of Medicine Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,9,9]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2018.09.086"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2014.09.019"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.13330"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.109.906610"},{"issue":"4","key":"e_1_2_7_6_1","first-page":"489","article-title":"Restoring pharmacologic preconditioning in the aging heart: role of mitophagy\/autophagy","volume":"72","author":"Ma L","year":"2017","journal-title":"J. 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