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

Publié dansThe Journal of biological chemistry, vol. 278, no. 45, p. 44769-44779
Date de publication2003
Résumé

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.

Mots-clés
  • Biological Transport/drug effects
  • Calcium/administration & dosage/metabolism
  • Calcium Channels/physiology
  • Calcium-Transporting ATPases/antagonists & inhibitors
  • Cell Membrane/physiology
  • Cells, Cultured
  • Clonazepam/analogs & derivatives/pharmacology
  • Electric Capacitance
  • Endoplasmic Reticulum/drug effects/metabolism
  • Endothelium, Vascular/ultrastructure
  • Histamine/pharmacology
  • Humans
  • Membrane Potentials
  • Mitochondria/metabolism/ultrastructure
  • Patch-Clamp Techniques
  • Sarcoplasmic Reticulum Calcium-Transporting ATPases
  • Signal Transduction
  • Sodium/administration & dosage
  • Sodium-Calcium Exchanger/antagonists & inhibitors/physiology
  • Thiazepines/pharmacology
  • Umbilical Veins
Citation (format ISO)
MALLI, Roland et al. Sustained Ca2+ transfer across mitochondria is Essential for mitochondrial Ca2+ buffering, sore-operated Ca2+ entry, and Ca2+ store refilling. In: The Journal of biological chemistry, 2003, vol. 278, n° 45, p. 44769–44779. doi: 10.1074/jbc.M302511200
Fichiers principaux (1)
Article (Published version)
accessLevelPublic
Identifiants
ISSN du journal0021-9258
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Informations techniques

Création10/10/2013 17:45:00
Première validation10/10/2013 17:45:00
Heure de mise à jour14/03/2023 20:32:51
Changement de statut14/03/2023 20:32:50
Dernière indexation16/01/2024 07:55:49
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