作者
Jing Qiu, Yan-Wei Tan, Anna M Hagenston, Marc-Andre Martel, Niclas Kneisel, Paul A Skehel, David JA Wyllie, Hilmar Bading, Giles E Hardingham
发表日期
2013/6/18
期刊
Nature communications
卷号
4
期号
1
页码范围
2034
出版商
Nature Publishing Group UK
简介
The recent identification of the mitochondrial Ca2+ uniporter gene (Mcu/Ccdc109a) has enabled us to address its role, and that of mitochondrial Ca2+ uptake, in neuronal excitotoxicity. Here we show that exogenously expressed Mcu is mitochondrially localized and increases mitochondrial Ca2+ levels following NMDA receptor activation, leading to increased mitochondrial membrane depolarization and excitotoxic cell death. Knockdown of endogenous Mcu expression reduces NMDA-induced increases in mitochondrial Ca2+, resulting in lower levels of mitochondrial depolarization and resistance to excitotoxicity. Mcu is subject to dynamic regulation as part of an activity-dependent adaptive mechanism that limits mitochondrial Ca2+ overload when cytoplasmic Ca2+ levels are high. Specifically, synaptic activity transcriptionally represses Mcu, via a mechanism involving the nuclear Ca2+ and CaM kinase-mediated …
学术搜索中的文章
J Qiu, YW Tan, AM Hagenston, MA Martel, N Kneisel… - Nature communications, 2013