Interplay Between Intracellular Ca(2+) Oscillations and Ca(2+)-stimulated Mitochondrial Metabolism

Scientific Reports
Benjamin WacquierGeneviève Dupont

Abstract

Oscillations of cytosolic Ca(2+) concentration are a widespread mode of signalling. Oscillatory spikes rely on repetitive exchanges of Ca(2+) between the endoplasmic reticulum (ER) and the cytosol, due to the regulation of inositol 1,4,5-trisphosphate receptors. Mitochondria also sequester and release Ca(2+), thus affecting Ca(2+) signalling. Mitochondrial Ca(2+) activates key enzymes involved in ATP synthesis. We propose a new integrative model for Ca(2+) signalling and mitochondrial metabolism in electrically non-excitable cells. The model accounts for (1) the phase relationship of the Ca(2+) changes in the cytosol, the ER and mitochondria, (2) the dynamics of mitochondrial metabolites in response to cytosolic Ca(2+) changes, and (3) the impacts of cytosol/mitochondria Ca(2+) exchanges and of mitochondrial metabolism on Ca(2+) oscillations. Simulations predict that as expected, oscillations are slowed down by decreasing the rate of Ca(2+) efflux from mitochondria, but also by decreasing the rate of Ca(2+) influx through the mitochondrial Ca(2+) uniporter (MCU). These predictions were experimentally validated by inhibiting MCU expression. Despite the highly non-linear character of Ca(2+) dynamics and mitochondrial metabolism, ...Continue Reading

References

Oct 11, 1994·Proceedings of the National Academy of Sciences of the United States of America·S SwillensP Champeil
Feb 24, 1997·The Journal of Cell Biology·D F BabcockB Hille
Aug 1, 1997·The American Journal of Physiology·G Magnus, J Keizer
May 12, 1998·The American Journal of Physiology·G Magnus, J Keizer
May 12, 1998·The American Journal of Physiology·G Magnus, J Keizer
Sep 2, 1998·The EMBO Journal·L D Robb-GaspersA P Thomas
Nov 26, 1999·Proceedings of the National Academy of Sciences of the United States of America·L S JouavilleR Rizzuto
May 24, 2001·Journal of Theoretical Biology·C P Fall, J E Keizer
Apr 2, 2003·Biophysical Journal·Sonia CortassaBrian O'Rourke
Jul 3, 2003·Nature Reviews. Molecular Cell Biology·Michael J BerridgeH Llewelyn Roderick
May 1, 1965·Journal of Molecular Biology·J MONODJ P CHANGEUX
Jan 15, 2004·The Journal of Biological Chemistry·George T HansonS James Remington
Aug 12, 2005·Annals of the New York Academy of Sciences·My-Hanh T Nguyen, M Saleet Jafri
May 25, 2006·Cell Calcium·Esther Hernández-SanMiguelJavier Alvarez
May 25, 2006·Chemistry & Biology·Amy E PalmerRoger Y Tsien
Sep 2, 2006·Journal of Theoretical Biology·Richard BertramArthur Sherman
Jan 24, 2007·Physiological Reviews·Jorgina SatrústeguiAraceli Del Arco
Apr 11, 2008·Physiology·György Szabadkai, Michael R Duchen
Jul 30, 2008·Cell·Wang WangHeping Cheng
Jan 16, 2009·Trends in Cell Biology·Teruo HayashiTsung-Ping Su
Jan 24, 2009·Biochimica Et Biophysica Acta·Thomas E Gunter, Shey-Shing Sheu
Apr 16, 2009·Biochimica Et Biophysica Acta·Elinor J Griffiths, Guy A Rutter
May 6, 2009·Biochimica Et Biophysica Acta·Richard M Denton
Jan 19, 2010·Biochimica Et Biophysica Acta·Jaime Santo-Domingo, Nicolas Demaurex
Mar 27, 2010·Biophysical Journal·Ranjan K PradhanRanjan K Dash
Aug 12, 2010·PLoS Computational Biology·Alexander SkupinMartin Falcke
Oct 5, 2010·HFSP Journal·Geneviève Dupont, Huguette Croisier
Mar 23, 2011·Cold Spring Harbor Perspectives in Biology·Geneviève DupontJames W Putney
Apr 15, 2011·ACS Chemical Biology·Masahiro NakanoHiroyuki Noji
Jul 7, 2011·PloS One·Jason N Bazil, Ranjan K Dash
Mar 27, 2012·Biochemistry·Brian Glancy, Robert S Balaban
Apr 20, 2012·Cell Calcium·Paolo Bernardi, Sophia von Stockum

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Citations

Feb 1, 2017·Journal of Molecular Biology·Alexander L Chernorudskiy, Ester Zito
Oct 22, 2017·The FEBS Journal·Benjamin WacquierGeneviève Dupont
Sep 16, 2016·F1000Research·Geneviève Dupont, Laurent Combettes
Nov 18, 2016·Open Biology·Roman UzhachenkoGeneviève Dupont
Aug 23, 2019·PLoS Computational Biology·Jung Min Han, Vipul Periwal
May 22, 2019·Cold Spring Harbor Perspectives in Biology·Benjamin WacquierGeneviève Dupont
Sep 12, 2019·Journal of Computational Neuroscience·Patrick Toglia, Ghanim Ullah
Nov 2, 2019·EMBO Reports·Arpit SharmaWilliam B Mair
Jul 16, 2020·PLoS Computational Biology·Shixin XuHuaxiong Huang
Jul 22, 2019·The Journal of General Physiology·Miriam BellPadmini Rangamani
Nov 21, 2019·Scientific Reports·Arash MoshkforoushB Rita Alevriadou
Mar 5, 2020·Scientific Reports·Benjamin WacquierGeneviève Dupont
May 1, 2018·Frontiers in Molecular Biosciences·Didier GonzeGeneviève Dupont
Aug 26, 2018·Nature Reviews. Molecular Cell Biology·Carlotta GiorgiPaolo Pinton
Nov 11, 2020·Interdisciplinary Sciences, Computational Life Sciences·Devanshi D Dave, Brajesh Kumar Jha
Jan 28, 2021·Genes·Ilaria Pontisso, Laurent Combettes
Sep 30, 2020·Nutrition Reviews·Frédéric N DaussinYan Burelle
Sep 25, 2018·Cell Calcium·Patrick TogliaGhanim Ullah
Apr 2, 2021·Journal of Theoretical Biology·Irina V DokukinaEugene A Grachev
Aug 22, 2021·Biophysical Chemistry·Igor Khmelinskii, Vladimir Makarov

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Methods Mentioned

BETA
fluorescence microscopy

Software Mentioned

XPPAUT
MATLAB solver
Compix
ode23

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