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| Item Type: | Article |
|---|---|
| Title: | Mitochondrial exchanger NCLX plays a major role in the intracellular Ca(2+) signaling, gliotransmission, and proliferation of astrocytes |
| Creators Name: | Parnis, J. and Montana, V. and Delgado-Martinez, I. and Matyash, V. and Parpura, V. and Kettenmann, H. and Sekler, I. and Nolte, C. |
| Abstract: | Mitochondria not only provide cells with energy, but are central to Ca(2+) signaling. Powered by the mitochondrial membrane potential, Ca(2+) enters the mitochondria and is released into the cytosol through a mitochondrial Na(+)/Ca(2+) exchanger. We established that NCLX, a newly discovered mitochondrial Na(+)/Ca(2+) exchanger, is expressed in astrocytes isolated from mice of either sex. Immunoblot analysis of organellar fractions showed that the location of NCLX is confined to mitochondria. Using pericam-based mitochondrial Ca(2+) imaging and NCLX inhibition either by siRNA or by the pharmacological blocker CGP37157, we demonstrated that NCLX is responsible for mitochondrial Ca(2+) extrusion. Suppression of NCLX function altered cytosolic Ca(2+) dynamics in astrocytes and this was mediated by a strong effect of NCLX activity on Ca(2+) influx via store-operated entry. Furthermore, Ca(2+) influx through the store-operated Ca(2+) entry triggered strong, whereas ER Ca(2+) release triggered only modest mitochondrial Ca(2+) transients, indicating that the functional cross talk between the plasma membrane and mitochondrial domains is particularly strong in astrocytes. Finally, silencing of NCLX expression significantly reduced Ca(2+)-dependent processes in astrocytes (i.e., exocytotic glutamate release, in vitro wound closure, and proliferation), whereas Ca(2+) wave propagation was not affected. Therefore, NCLX, by meditating astrocytic mitochondrial Na(+)/Ca(2+) exchange, links between mitochondria and plasma membrane Ca(2+) signaling, thereby modulating cytoplasmic Ca(2+) transients required to control a diverse array of astrocyte functions. |
| Keywords: | Astrocytes, Calcium Signaling, Cell Proliferation, Cultured Cells, Intracellular Fluid, Mitochondria, Neuroglia, Sodium-Calcium Exchanger, Synaptic Transmission, Animals, Mice |
| Source: | Journal of Neuroscience |
| ISSN: | 0270-6474 |
| Publisher: | Society for Neuroscience |
| Volume: | 33 |
| Number: | 17 |
| Page Range: | 7206-7219 |
| Date: | 24 April 2013 |
| Official Publication: | https://doi.org/10.1523/JNEUROSCI.5721-12.2013 |
| PubMed: | View item in PubMed |
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