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Subplasmalemmal mitochondria modulate the activity of plasma membrane Ca2+-ATPases

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Published in Journal of Biological Chemistry. 2005, vol. 280, no. 52, p. 43198-208
Abstract Mitochondria are dynamic organelles that modulate cellular Ca2+ signals by interacting with Ca2+ transporters on the plasma membrane or the endoplasmic reticulum (ER). To study how mitochondria dynamics affects cell Ca2+ homeostasis, we overexpressed two mitochondrial fission proteins, hFis1 and Drp1, and measured Ca2+ changes within the cytosol and the ER in HeLa cells. Both proteins fragmented mitochondria, decreased their total volume by 25-40%, and reduced the fraction of subplasmalemmal mitochondria by 4-fold. The cytosolic Ca2+ signals elicited by histamine were unaltered in cells lacking subplasmalemmal mitochondria as long as Ca2+ was present in the medium, but the signals were significantly blunted when Ca2+ was removed. Upon Ca2+ withdrawal, the free ER Ca2+ concentration decreased rapidly, and hFis1 cells were unable to respond to repetitive histamine stimulations. The loss of stored Ca2+ was due to an increased activity of plasma membrane Ca2+-ATPase (PMCA) pumps and was associated with an increased influx of Ca2+ and Mn2+ across store-operated Ca2+ channels. The increased Ca2+ influx compensated for the loss of stored Ca2+, and brief Ca2+ additions between successive agonist stimulations fully corrected subsequent histamine responses. We propose that the lack of subplasmalemmal mitochondria disrupts the transfer of Ca2+ from plasma membrane channels to the ER and that the resulting increase in subplasmalemmal [Ca2+] up-regulates the activity of PMCA. The increased Ca2+ extrusion promotes ER depletion and the subsequent activation of store-operated Ca2+ channels. Cells thus adapt to the lack of subplasmalemmal mitochondria by relying on external rather than on internal Ca2+ for signaling.
Keywords Calcium/metabolismCalcium-Transporting ATPases/physiologyCation Transport Proteins/physiologyCell Membrane/metabolismCytosol/metabolismDNA, Complementary/metabolismEndoplasmic Reticulum/metabolismHeLa CellsHistamine/metabolismHomeostasisHumansManganese/metabolismMembrane ProteinsMicroscopy, FluorescenceMitochondria/metabolismMitochondrial Proteins/physiologyModels, BiologicalNerve Tissue Proteins/metabolism/physiologyPlasma Membrane Calcium-Transporting ATPasesSignal TransductionTime FactorsTransfection
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PMID: 16216868
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Article (Published version) (954 Kb) - public document Free access
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Research group Signaux intracellulaires (210)
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FRIEDEN, Maud et al. Subplasmalemmal mitochondria modulate the activity of plasma membrane Ca2+-ATPases. In: Journal of Biological Chemistry, 2005, vol. 280, n° 52, p. 43198-208. https://archive-ouverte.unige.ch/unige:30419

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Deposited on : 2013-10-16

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