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| Verfasst von: | Qiu, Jing [VerfasserIn]  |
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| | Tan, Yan-Wei [VerfasserIn] |
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| | Hertle, Anna M. [VerfasserIn] |
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| | Martel, Marc-Andre [VerfasserIn] |
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| | Kneisel, Niclas [VerfasserIn] |
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| | Skehel, Paul A. [VerfasserIn] |
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| | Wyllie, David J. A. [VerfasserIn] |
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| | Bading, Hilmar [VerfasserIn] |
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| | Hardingham, Giles E. [VerfasserIn] |
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| Titel: | Mitochondrial calcium uniporter Mcu controls excitotoxicity and is transcriptionally repressed by neuroprotective nuclear calcium signals |
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| Verf.angabe: | Jing Qiu, Yan-Wei Tan, Anna M. Hagenston, Marc-Andre Martel, Niclas Kneisel, Paul A. Skehel, David J.A. Wyllie, Hilmar Bading & Giles E. Hardingham |
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| E-Jahr: | 2013 |
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| Jahr: | 18 Jun 2013 |
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| Umfang: | 12 S. |
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| Fussnoten: | Gesehen am 05.01.2022 |
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| Titel Quelle: | Enthalten in: Nature Communications |
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| Ort Quelle: | [London] : Nature Publishing Group UK, 2010 |
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| Jahr Quelle: | 2013 |
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| Band/Heft Quelle: | 4(2013), Artikel-ID 2034, Seite 1-12 |
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| ISSN Quelle: | 2041-1723 |
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| Abstract: | 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 induction of Npas4, resulting in the inhibition of NMDA receptor-induced mitochondrial Ca2+ uptake and preventing excitotoxic death. This establishes Mcu and the pathways regulating its expression as important determinants of excitotoxicity, which may represent therapeutic targets for excitotoxic disorders. |
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| DOI: | doi:10.1038/ncomms3034 |
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| URL: | Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.
Volltext ; Verlag: https://doi.org/10.1038/ncomms3034 |
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| | Volltext: https://www.nature.com/articles/ncomms3034 |
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| | DOI: https://doi.org/10.1038/ncomms3034 |
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| Datenträger: | Online-Ressource |
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| Sprache: | eng |
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| Sach-SW: | Calcium signalling |
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| | Neuroscience |
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| K10plus-PPN: | 1784826359 |
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| Verknüpfungen: | → Zeitschrift |
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Mitochondrial calcium uniporter Mcu controls excitotoxicity and is transcriptionally repressed by neuroprotective nuclear calcium signals / Qiu, Jing [VerfasserIn]; 18 Jun 2013 (Online-Ressource)
