The effect of mitochondrial calcium uniporter on mitochondrial fission in hippocampus cells ischemia/reperfusion injury.
The mitochondrial calcium uniporter (MCU) transports free Ca(2+) into the mitochondrial matrix, maintaining Ca(2+) homeostasis, thus regulates the mitochondrial morphology. Previous studies have indicated that there was closely crosstalk between MCU 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 Ca(2+) 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 Ca(2+) 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.
Department of Anesthesiology, Affiliated Hospital of Qingdao University, Qingdao 266003, Shandong, China.
Lantao
L
Zhao
Department of Anesthesiology, Affiliated Hospital of Qingdao University, Qingdao 266003, Shandong, China.
Shuhong
S
Li
Department of Anesthesiology, Affiliated Hospital of Qingdao University, Qingdao 266003, Shandong, China. Electronic address: wshlei@aliyun.com.
Shilei
S
Wang
Department of Anesthesiology, Affiliated Hospital of Qingdao University, Qingdao 266003, Shandong, China.
Ning
N
Yu
Department of Anesthesiology, Affiliated Hospital of Qingdao University, Qingdao 266003, Shandong, China.
Jia
J
Liu
D000818:Animals; D015220:Calcium Channels / Q000502:physiology*; D006624:Hippocampus / Q000503:physiopathology*; D008928:Mitochondria / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000503:physiopathology*
D015220:Calcium Channels; C034703:mitochondrial calcium uniporter
Fis1; Ischemia/reperfusion injury; MCU; MIEF1; Mitochondrial calcium; Mitochondrial fission