Journal article

Routes of Ca²⁺ shuttling during Ca²⁺ oscillations FOCUS ON THE ROLE OF MITOCHONDRIAL Ca²⁺ HANDLING AND CYTOSOLIC Ca²⁺ BUFFERS

  • Pecze, László Anatomy, Department of Medicine, University of Fribourg, Switzerland
  • Blum, Walter Anatomy, Department of Medicine, University of Fribourg, Switzerland
  • Schwaller, Beat Anatomy, Department of Medicine, University of Fribourg, Switzerland
Published in:
  • Journal of Biological Chemistry. - 2015, vol. 290, no. 47, p. 28214–28230
English In some cell types, Ca²⁺ oscillations are strictly dependent on Ca²⁺ influx across the plasma membrane, whereas in others, oscillations also persist in the absence of Ca²⁺ influx. We observed that, in primary mesothelial cells, the plasmalemmal Ca²⁺ influx played a pivotal role. However, when the Ca²⁺ transport across the plasma membrane by the “lanthanum insulation method” was blocked prior to the induction of the serum-induced Ca²⁺ oscillations, mitochondrial Ca²⁺ transport was found to be able to substitute for the plasmalemmal Ca²⁺ exchange function, thus rendering the oscillations independent of extracellular Ca²⁺. However, in a physiological situation, the Ca²⁺-buffering capacity of mitochondria was found not to be essential for Ca²⁺ oscillations. Moreover, brief spontaneous Ca²⁺ changes were observed in the mitochondrial Ca²⁺ concentration without apparent changes in the cytosolic Ca²⁺ concentration, indicating the presence of a mitochondrial autonomous Ca²⁺ signaling mechanism. In the presence of calretinin, a Ca²⁺-buffering protein, the amplitude of cytosolic spikes during oscillations was decreased, and the amount of Ca²⁺ ions taken up by mitochondria was reduced. Thus, the increased calretinin expression observed in mesothelioma cells and in certain colon cancer might be correlated to the increased resistance of these tumor cells to proapoptotic/pronecrotic signals. We identified and characterized (experimentally and by modeling) three Ca²⁺ shuttling pathways in primary mesothelial cells during Ca²⁺ oscillations: Ca²⁺ shuttled between (i) the endoplasmic reticulum (ER) and mitochondria, (ii) the ER and the extracellular space, and (iii) the ER and cytoplasmic Ca²⁺ buffers.
Faculté des sciences et de médecine
Département de Médecine
  • English
Biological sciences
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