The effect of mitochondrial calcium uniporter on mitochondrial fission in hippocampus cells ischemia/reperfusion injury

被引:88
作者
Zhao, Lantao [1 ]
Li, Shuhong [1 ]
Wang, Shilei [1 ]
Yu, Ning [1 ]
Liu, Jia [1 ]
机构
[1] Qingdao Univ, Affiliated Hosp, Dept Anesthesiol, Qingdao 266003, Shandong, Peoples R China
基金
中国国家自然科学基金;
关键词
Ischemia/reperfusion injury; MCU; Mitochondrial fission; Mitochondrial calcium; MIEF1; Fis1; DRP1; APOPTOSIS; DYNAMICS; PHOSPHORYLATION; COMPONENT; DIVISION; FUSION; KINASE; HFIS1; MIEF1;
D O I
10.1016/j.bbrc.2015.04.066
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
070307 [化学生物学]; 071010 [生物化学与分子生物学];
摘要
The mitochondrial calcium uniporter (MCU) transports free Ca2+ into the mitochondrial matrix, maintaining Ca2+ homeostasis, thus regulates the mitochondrial morphology. Previous studies have indicated that there was closely crosstalk between MW and mitochondrial fission during the process of ischemia/reperfusion injury. This study constructed a hypoxia reoxygenation model using primary hippocampus neurons to mimic the cerebral ischemia/reperfusion injury and aims to explore the exactly effect of MCU on the mitochondrial fission during the process of ischemia/reperfusion injury and so as the mechanisms. Our results found that the inhibitor of the MCU, Ru360, decreased mitochondrial Ca2+ concentration, suppressed the expression of mitochondrial fission protein Drp1, MIEF1 and Fis1, and thus improved mitochondrial morphology significantly. Whereas spermine, the agonist of the MCU, had no significant impact compared to the I/R group. This study demonstrated that the MCU regulates the process of mitochondrial fission by controlling the Ca2+ transport, directly upregulating mitochondrial fission proteins Drp1, Fis1 and indirectly reversing the MIEF1-induced mitochondrial fusion. It also provides new targets for brain protection during ischemia/reperfusion injury. (C) 2015 Elsevier Inc. All rights reserved.
引用
收藏
页码:537 / 542
页数:6
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