Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Malli, R; Frieden, M; Osibow, K; Zoratti, C; Mayer, M; Demaurex, N; Graier, WF.
Sustained Ca2+ transfer across mitochondria is Essential for mitochondrial Ca2+ buffering, sore-operated Ca2+ entry, and Ca2+ store refilling.
J Biol Chem. 2003; 278(45):44769-44779
Doi: 10.1074/jbc.M302511200
[OPEN ACCESS]
Web of Science
PubMed
FullText
FullText_MUG
Google Scholar
- Führende Autor*innen der Med Uni Graz
- Graier Wolfgang
- Malli Roland
- Co-Autor*innen der Med Uni Graz
- Osibow Karin
- Altmetrics:
- Dimensions Citations:
- Plum Analytics:
- Scite (citation analytics):
- 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.
- Find related publications in this database (using NLM MeSH Indexing)
- Biological Transport - drug effects
- Calcium - administration and dosage
- Calcium Channels - physiology
- Calcium-Transporting ATPases - antagonists and inhibitors
- Cell Membrane - physiology
- Cells, Cultured - physiology
- Clonazepam - analogs and derivatives
- Electric Capacitance - analogs and derivatives
- Endoplasmic Reticulum - drug effects
- Endothelium, Vascular - ultrastructure
- Histamine - pharmacology
- Humans - pharmacology
- Membrane Potentials - pharmacology
- Mitochondria - metabolism
- Patch-Clamp Techniques - metabolism
- Sarcoplasmic Reticulum Calcium-Transporting ATPases - metabolism
- Signal Transduction - metabolism
- Sodium - administration and dosage
- Sodium-Calcium Exchanger - antagonists and inhibitors
- Thiazepines - pharmacology
- Umbilical Veins - pharmacology