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Sustained Ca2+ transfer across mitochondria is Essential for mitochondrial Ca2+ buffering, sore-operated Ca2+ entry, and Ca2+ store refilling

Malli, Roland
Osibow, Karin
Zoratti, Cristina
Mayer, Mirza
Graier, Wolfgang F
Published in Journal of Biological Chemistry. 2003, vol. 278, no. 45, p. 44769-79
Abstract Mitochondria have been found to sequester and release Ca2+ during cell stimulation with inositol 1,4,5-triphosphate-generating agonists, thereby generating subplasmalemmal microdomains of low Ca2+ that sustain activity of capacitative Ca2+ entry (CCE). Procedures that prevent mitochondrial Ca2+ uptake inhibit local Ca2+ buffering and CCE, but it is not clear whether Ca2+ has to transit through or remains trapped in the mitochondria. Thus, we analyzed the contribution of mitochondrial Ca2+ efflux on the ability of mitochondria to buffer subplasmalemmal Ca2+, to maintain CCE, and to facilitate endoplasmic reticulum (ER) refilling in endothelial cells. Upon the addition of histamine, the initial mitochondrial Ca2+ transient, monitored with ratio-metric-pericam-mitochondria, was largely independent of extracellular Ca2+. However, subsequent removal of extracellular Ca2+ produced a reversible decrease in [Ca2+]mito, indicating that Ca2+ was continuously taken up and released by mitochondria, although [Ca2+]mito had returned to basal levels. Accordingly, inhibition of the mitochondrial Na+/Ca2+ exchanger with CGP 37157 increased [Ca2+]mito and abolished the ability of mitochondria to buffer subplasmalemmal Ca2+, resulting in an increased activity of BKCa channels and a decrease in CCE. Hence, CGP 37157 also reversibly inhibited ER refilling during cell stimulation. These effects of CGP 37157 were mimicked if mitochondrial Ca2+ uptake was prevented with oligomycin/antimycin A. Thus, during cell stimulation a continuous Ca2+ flux through mitochondria underlies the ability of mitochondria to generate subplasmalemmal microdomains of low Ca2+, to facilitate CCE, and to relay Ca2+ from the plasma membrane to the ER.
Keywords Biological Transport/drug effectsCalcium/administration & dosage/metabolismCalcium Channels/physiologyCalcium-Transporting ATPases/antagonists & inhibitorsCell Membrane/physiologyCells, CulturedClonazepam/analogs & derivatives/pharmacologyElectric CapacitanceEndoplasmic Reticulum/drug effects/metabolismEndothelium, Vascular/ultrastructureHistamine/pharmacologyHumansMembrane PotentialsMitochondria/metabolism/ultrastructurePatch-Clamp TechniquesSarcoplasmic Reticulum Calcium-Transporting ATPasesSignal TransductionSodium/administration & dosageSodium-Calcium Exchanger/antagonists & inhibitors/physiologyThiazepines/pharmacologyUmbilical Veins
PMID: 12941956
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Research group Signaux intracellulaires (210)
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MALLI, Roland et al. Sustained Ca2+ transfer across mitochondria is Essential for mitochondrial Ca2+ buffering, sore-operated Ca2+ entry, and Ca2+ store refilling. In: Journal of Biological Chemistry, 2003, vol. 278, n° 45, p. 44769-79. https://archive-ouverte.unige.ch/unige:30407

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Deposited on : 2013-10-15

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