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Zinc plays a role in mitophagy and protects cardiomyocytes from ischemia\/reperfusion injury. This study is aimed at investigating whether SUMOylation of Drp1 is involved in the protection of zinc ion on cardiac I\/R injury. <jats:italic>Methods<\/jats:italic>. Mouse hearts were subjected to 30 minutes of regional ischemia followed by 2 hours of reperfusion (ischemia\/reoxygenation (I\/R)). Infarct size and apoptosis were assessed. HL-1 cells were subjected to 24 hours of hypoxia and 6 hours of reoxygenation (hypoxia\/reoxygenation (H\/R)). Zinc was given 5\u2009min before reperfusion for 30\u2009min. SENP2 overexpression plasmid (Flag-SENP2), Drp1 mutation plasmid (Myc-Drp1 4KR), and SUMO1 siRNA were transfected into HL-1 cells for 48\u2009h before hypoxia. Effects of zinc on SUMO family members were analyzed by Western blotting. SUMOylation of Drp1, apoptosis and the collapse of mitochondrial membrane potential (<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M1\"><mml:mi>\u0394<\/mml:mi><mml:mi>\u03a8<\/mml:mi><mml:mtext>m<\/mml:mtext><\/mml:math>), and mitophagy were evaluated. <jats:italic>Results<\/jats:italic>. Compared with the control, SUMO1 modification level of proteins in the H\/R decreased, while this effect was reversed by zinc. In the setting of H\/R, zinc attenuated myocardial apoptosis, which was reversed by SUMO1 siRNA. Similar effects were observed in SUMO1 KO mice exposed to H\/R. In addition, the dynamin-related protein 1 (Drp1) is a target protein of SUMO1. The SUMOylation of Drp1 induced by zinc regulated mitophagy and contributed to the protective effect of zinc on H\/R injury. <jats:italic>Conclusions<\/jats:italic>. SUMOylation of Drp1 played an essential role in zinc-induced cardio protection against I\/R injury. Our findings provide a promising therapeutic approach for acute myocardial I\/R injury.<\/jats:p>","DOI":"10.1155\/2019\/1232146","type":"journal-article","created":{"date-parts":[[2019,7,22]],"date-time":"2019-07-22T19:30:32Z","timestamp":1563823832000},"page":"1-11","source":"Crossref","is-referenced-by-count":43,"title":["Zinc-Induced SUMOylation of Dynamin-Related Protein 1 Protects the Heart against Ischemia-Reperfusion Injury"],"prefix":"10.1155","volume":"2019","author":[{"given":"Xiyun","family":"Bian","sequence":"first","affiliation":[{"name":"Central Laboratory, The Fifth Central Hospital of Tianjin, Tianjin 300450, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingman","family":"Xu","sequence":"additional","affiliation":[{"name":"Medical Research Center, North China University of Science and Technology, Tangshan 063000, 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