EMRE Is a Matrix Ca(2+) Sensor that Governs Gatekeeping of the Mitochondrial Ca(2+) Uniporter

Cell Reports
Horia VaisJ Kevin Foskett

Abstract

The mitochondrial uniporter (MCU) is an ion channel that mediates Ca(2+) uptake into the matrix to regulate metabolism, cell death, and cytoplasmic Ca(2+) signaling. Matrix Ca(2+) concentration is similar to that in cytoplasm, despite an enormous driving force for entry, but the mechanisms that prevent mitochondrial Ca(2+) overload are unclear. Here, we show that MCU channel activity is governed by matrix Ca(2+) concentration through EMRE. Deletion or charge neutralization of its matrix-localized acidic C terminus abolishes matrix Ca(2+) inhibition of MCU Ca(2+) currents, resulting in MCU channel activation, enhanced mitochondrial Ca(2+) uptake, and constitutively elevated matrix Ca(2+) concentration. EMRE-dependent regulation of MCU channel activity requires intermembrane space-localized MICU1, MICU2, and cytoplasmic Ca(2+). Thus, mitochondria are protected from Ca(2+) depletion and Ca(2+) overload by a unique molecular complex that involves Ca(2+) sensors on both sides of the inner mitochondrial membrane, coupled through EMRE.

References

Dec 25, 1979·Biochemistry·M BragadinG F Azzone
Oct 1, 1982·European Journal of Biochemistry·F Zoccarato, D Nicholls
Jan 23, 2004·Nature·Yuriy KirichokDavid E Clapham
May 25, 2006·Chemistry & Biology·Amy E PalmerRoger Y Tsien
Mar 21, 2009·Biochimica Et Biophysica Acta·David G Nicholls
Jan 10, 2012·Biochimica Et Biophysica Acta·Carl Christel, Amy Lee
Dec 29, 2012·Nature Communications·Francesca FieniYuriy Kirichok
May 6, 2014·Biochemical and Biophysical Research Communications·Diego De Stefani, Rosario Rizzuto
May 13, 2014·Biochemical and Biophysical Research Communications·Kimberli J KamerVamsi K Mootha
Sep 18, 2014·Biophysical Journal·Liron BoymanW Jonathan Lederer
Oct 9, 2015·Cell Metabolism·Horia VaisJ Kevin Foskett

❮ Previous
Next ❯

Citations

Mar 24, 2016·Biochimica Et Biophysica Acta·Takenori YamamotoYasuo Shinohara
Apr 12, 2016·Frontiers in Plant Science·Luca CarrarettoEnrico Teardo
Mar 24, 2016·Journal of Experimental Botany·Stephan WagnerIldikò Szabò
Jul 6, 2016·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Ole H Petersen, Alexei Verkhratsky
Jul 6, 2016·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Shuang PengOleg V Gerasimenko
Sep 20, 2016·Nature Communications·Corina T Madreiter-SokolowskiWolfgang F Graier
Oct 4, 2016·Trends in Biochemical Sciences·Anna RaffaelloRosario Rizzuto
Dec 20, 2016·The Journal of Physiology·Jennifer Q Kwong
Mar 17, 2018·Genes·Corina T Madreiter-SokolowskiWolfgang F Graier
Apr 29, 2016·American Journal of Physiology. Cell Physiology·Bong Sook JhunJin O-Uchi
Dec 15, 2017·Journal of the Royal Society, Interface·B Rita AlevriadouMuniswamy Madesh
Oct 21, 2017·Brain : a Journal of Neurology·Hanan E ShamseldinFowzan S Alkuraya
Jan 11, 2018·The Journal of Physiology·Daniela M Arduino, Fabiana Perocchi
Sep 16, 2018·The Journal of Physiology·Pei WangShey-Shing Sheu
Sep 16, 2016·F1000Research·Geneviève Dupont, Laurent Combettes
Nov 16, 2018·British Journal of Pharmacology·Luigi LeanzaIldiko Szabo
Aug 21, 2019·Nature Communications·Benjamin GottschalkWolfgang F Graier
Dec 6, 2019·Journal of the American Heart Association·Hemanth N BanavathSamarjit Das
Jul 17, 2019·Cold Spring Harbor Perspectives in Biology·Guillaume GilbertH Llewelyn Roderick
Mar 5, 2020·Proteomics·Venkateswaran NatarajanKarthik Mallilankaraman
Jun 13, 2018·The Journal of General Physiology·Chen-Wei Tsai, Ming-Feng Tsai
Mar 16, 2018·Pflügers Archiv : European journal of physiology·Cristina MammucariRosario Rizzuto
Dec 18, 2018·F1000Research·Giorgia PallafacchinaRosario Rizzuto
Jun 11, 2019·Oxidative Medicine and Cellular Longevity·Simona FenoAnna Raffaello
Oct 30, 2016·The Journal of Biological Chemistry·Sergio De La FuenteGyörgy Csordás
May 19, 2017·Frontiers in Oncology·Hristina IvanovaGeert Bultynck
Jul 26, 2017·Frontiers in Oncology·Cristina MammucariRosario Rizzuto
Aug 31, 2018·Nature Communications·Santhanam ShanmughapriyaMuniswamy Madesh
Sep 23, 2018·Scientific Reports·Alessandra MatteucciTito Calì
Nov 7, 2019·Cell Death and Differentiation·Nicoletta PlotegherMichael R Duchen
Apr 25, 2020·Frontiers in Physiology·Devasena Ponnalagu, Harpreet Singh
Aug 10, 2020·Life Science Alliance·Melissa Js MacEwenYasemin Sancak
Aug 26, 2018·Nature Reviews. Molecular Cell Biology·Carlotta GiorgiPaolo Pinton
Dec 10, 2016·Frontiers in Physiology·Paolo Bernardi, Michael Forte
Jun 27, 2019·Biochemistry. Biokhimii︠a︡·K N BelosludtsevG D Mironova
May 28, 2020·International Journal of Molecular Sciences·Megan NoblePeter B Stathopulos
Aug 18, 2020·Proceedings of the National Academy of Sciences of the United States of America·Horia VaisJ Kevin Foskett

❮ Previous
Next ❯

Related Concepts

Related Feeds

Calcium & Bioenergetics

Bioenergetic processes, including cellular respiration and photosynthesis, concern the transformation of energy by cells. Here is the latest research on the role of calcium in bioenergetics.