Mitochondrial exchanger NCLX plays a major role in the intracellular Ca2+ signaling, gliotransmission, and proliferation of astrocytes.
J Neurosci
; 33(17): 7206-19, 2013 Apr 24.
Article
em En
| MEDLINE
| ID: mdl-23616530
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.
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Base de dados:
MEDLINE
Assunto principal:
Neuroglia
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Astrócitos
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Transmissão Sináptica
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Trocador de Sódio e Cálcio
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Sinalização do Cálcio
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Proliferação de Células
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Mitocôndrias
Limite:
Animals
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article