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Mitochondrial exchanger NCLX plays a major role in the intracellular Ca(2+) signaling, gliotransmission, and proliferation of astrocytes

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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 (U.S.A.)
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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