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NCLX is an essential component of mitochondrial Na+/Ca2+ exchange

Item Type:Article
Title:NCLX is an essential component of mitochondrial Na+/Ca2+ exchange
Creators Name:Palty, R. and Silverman, W.F. and Hershfinkel, M. and Caporale, T. and Sensi, S.L. and Parnis, J. and Nolte, C. and Fishman, D. and Shoshan-Barmatz, V. and Herrmann, S. and Khananshvili, D. and Sekler, I.
Abstract:Mitochondrial Ca(2+) efflux is linked to numerous cellular activities and pathophysiological processes. Although it is established that an Na(+)-dependent mechanism mediates mitochondrial Ca(2+) efflux, the molecular identity of this transporter has remained elusive. Here we show that the Na(+)/Ca(2+) exchanger NCLX is enriched in mitochondria, where it is localized to the cristae. Employing Ca(2+) and Na(+) fluorescent imaging, we demonstrate that mitochondrial Na(+)-dependent Ca(2+) efflux is enhanced upon overexpression of NCLX, is reduced by silencing of NCLX expression by siRNA, and is fully rescued by the concomitant expression of heterologous NCLX. NCLX-mediated mitochondrial Ca(2+) transport was inhibited, moreover, by CGP-37157 and exhibited Li(+) dependence, both hallmarks of mitochondrial Na(+)-dependent Ca(2+) efflux. Finally, NCLX-mediated mitochondrial Ca(2+) exchange is blocked in cells expressing a catalytically inactive NCLX mutant. Taken together, our results converge to the conclusion that NCLX is the long-sought mitochondrial Na(+)/Ca(2+) exchanger.
Keywords:Mitochondrial Calcium Exchanger, Mitochondrial Calcium Homeostasis, Sodium Calcium Exchanger, CGP-37157, Animals, Mice, Rats
Source:Proceedings of the National Academy of Sciences of the United States of America
ISSN:0027-8424
Publisher:National Academy of Sciences (U.S.A.)
Volume:107
Number:1
Page Range:436-441
Date:5 January 2010
Official Publication:https://doi.org/10.1073/pnas.0908099107
PubMed:View item in PubMed

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