Inhibition of mitochondrial calcium uniporter protects neurocytes from ischemia/reperfusion injury via the inhibition of excessive mitophagy.
Mitophagy plays an important role in mitochondrial quality control and cell survival during the process of ischemia/reperfusion (I/R) injury. Mitochondrial calcium uniporter (MCU) is the most important channel responsible for Ca(2+) influx into mitochondria and Ca(2+) signal plays a potential role in modulating mitophagy. However, the effect of MCU on mitophagy during the process of I/R injury remains unknown. This study constructed an in vitro I/R model by subjecting oxygen and glucose deprivation/reperfusion (OGD/RP) model to SH-SY5Y cells to mimic the cerebral I/R injury and aimed to explore the exact effect of MCU on I/R induced mitophagy. The results showed that OGD/RP induced autophagy and mitophagy in SH-SY5Y cells. Ru360, the inhibitor of MCU, improved mitochondrial morphology and fuctional stability as well as cell viability, significantly reduced OGD/RP induced mitophagy as evidenced by the decrease in Beclin-1 and the increase in Tom20 and P62 expression. Whereas spermine, the agonist of MCU, had no significant impact on the expression of those mitophagy related proteins compared with OGD/RP group. This study indicates that inhibition of MCU can inhibit excessive mitophagy and protect the neurocytes from I/R injury.
Qingdao University, Qingdao 266003, Shandong, China; Department of Anesthesiology, Rizhao People's Hospital, Rizhao 276800, Shandong, China.
Shoushui
S
Yu
Department of Anesthesiology, Rizhao People's Hospital, Rizhao 276800, Shandong, China.
Shengfa
S
Zheng
Department of Anesthesiology, Rizhao People's Hospital, Rizhao 276800, Shandong, China.
Jing
J
Leng
Department of Anesthesiology, Affiliated Hospital of Qingdao University, Huangdao, Qingdao 266003, Shandong, China. Electronic address: wshlei@aliyun.com.
Shilei
S
Wang
Department of Anesthesiology, Rizhao People's Hospital, Rizhao 276800, Shandong, China.
Tao
T
Zhao
Department of Anesthesiology, Affiliated Hospital of Qingdao University, Huangdao, Qingdao 266003, Shandong, China.
Jia
J
Liu
D001343:Autophagy / Q000187:drug effects; D000071186:Beclin-1 / Q000378:metabolism; D015220:Calcium Channels / Q000502:physiology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D026901:Membrane Transport Proteins / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D063306:Mitophagy / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D016601:RNA-Binding Proteins / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D015427:Reperfusion Injury / Q000378:metabolism / Q000503:physiopathology*; D017975:Ruthenium Compounds / Q000494:pharmacology; D013096:Spermine / Q000494:pharmacology
C491997:BECN1 protein, human; D000071186:Beclin-1; D015220:Calcium Channels; D026901:Membrane Transport Proteins; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; C118585:P62 protein, human; D016601:RNA-Binding Proteins; D011956:Receptors, Cell Surface; C112020:Ru 360; D017975:Ruthenium Compounds; C084008:TOMM20 protein, human; C034703:mitochondrial calcium uniporter; D013096:Spermine
Ischemia/reperfusion injury; MCU; Mitophagy; Neuroprotection