MiP2005: Session 3 - Young Investigator Presentation
Mitochondrial Physiology Network 10.9: 41 (2005) - download pdf
The ER Ca2+-pumps and the mitochondrial Na+/Ca2+-exchange function in a close relationship of interdependency.
Michael Trenker1, M Weiermair1, M Frieden2, R Malli1, WF Graier1
1Department of Molecular Biology and Biochemistry, Center of Molecular Medicine, Medical University of Graz, Harrachgasse 21/III, A-8010 Graz, Austria; 2Department of Cell Physiology and Metabolism, University of Geneva, Medical Center, 1211 Geneva 4, Switzerland. - firstname.lastname@example.org
Intracellular Ca2+ controls a remarkable number of signalling pathways within cells. The question is how signalling specificity is maintained with the use of such a promiscuous messenger. In many cells spatial and temporal Ca2+ gradients are dynamically generated and thought to play crucial roles in achieving signalling specificity . Growing evidence suggests that local Ca2+ communication between the endoplasmic reticulum (ER) and mitochondria is of utmost importance for the formation, maintenance and control of specific local Ca2+ microdomains within a cell. However, the molecular mechanisms of Ca2+ signal transmission between these organelles are only fractionally decoded and thus still subject of acute research . Recently we showed that mitochondria deliver extracellular Ca2+ towards the ER Ca2+ pumps (SERCAs) during cell stimulation with an IP3-generating agonist . Thereby mitochondria seem to imbibe Ca2+ close to Ca2+ entry channels at the plasma membrane and subsequently release the absorbed Ca2+ via the mitochondrial Na+/Ca2+-exchanger (NCXmito). Inhibition of NCXmito using the benzothiazepin derivate CGP 37157 prevented complete Ca2+ refilling of the ER during cell stimulation. In addition, SERCA inhibition during cell stimulation with an IP3-generating agonist increased mitochondrial Ca2+ concentration ([Ca2+]mito) at once. This effect was clearly attenuated by NCXmito inhibition indicating that the mitochondrial Ca2+ elevation upon SERCA inhibition is accomplished by the NCXmito working in reversed mode. In addition this result implicates that the ER Ca2+ pumps function in a close relationship of interdependency to the NCXmito. Thus it is tempting to speculate, that both Ca2+ transporters located at different organelles are also physically linked (see figure) at least during cell stimulation. Such a coupling of these proteins might be accomplished by yet unknown scaffolding-, anchoring- or adaptor-proteins and may explain the observed functional interdependency.
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3. Malli R, Frieden M, Trenker M, Graier WF (2005). The role of mitochondria for Ca2+ refilling of the endoplasmic reticulum. J. Biol. Chem. 280: 12114-12122.