1. Inhibition of mitochondrial calcium uniporter protects neurocytes from ischemia/reperfusion injury via the inhibition of excessive mitophagy.
- Author
-
Yu S, Zheng S, Leng J, Wang S, Zhao T, and Liu J
- Subjects
- Autophagy drug effects, Beclin-1 metabolism, Cell Line, Tumor, Cell Survival drug effects, Humans, Membrane Transport Proteins metabolism, Mitochondria drug effects, Mitochondria ultrastructure, Mitochondrial Precursor Protein Import Complex Proteins, Neurons drug effects, Neurons metabolism, Neurons ultrastructure, RNA-Binding Proteins metabolism, Receptors, Cell Surface metabolism, Reperfusion Injury metabolism, Ruthenium Compounds pharmacology, Spermine pharmacology, Calcium Channels physiology, Mitochondria physiology, Mitophagy drug effects, Neurons physiology, Reperfusion Injury physiopathology
- Abstract
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., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)
- Published
- 2016
- Full Text
- View/download PDF