NCLX is an essential component of mitochondrial Na+/Ca 2+ exchange

Raz Palty, William F. Silverman, Michal Hershfinkel, Teresa Caporale, Stefano L. Sensi, Julia Parnis, Christiane Nolte, Daniel Fishman, Varda Shoshan-Barmatz, Sharon Herrmann, Daniel Khananshvili, Israel Sekler*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Mitochondrial Ca2+ efflux is linked to numerous cellular activities and pathophysiological processes. Although it is established that an Na+-dependent mechanism mediates mitochondrial Ca2+ efflux, the molecular identity of this transporter has remained elusive. Here we show that the Na+/Ca2+ exchanger NCLX is enriched in mitochondria, where it is localized to the cristae. Employing Ca2+ and Na+ fluorescent imaging, we demonstrate that mitochondrial Na+-dependent Ca2+ 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 Ca2+ transport was inhibited, moreover, by CGP-37157 and exhibited Li+ dependence, both hall-marks of mitochondrial Na+-dependent Ca2+ efflux. Finally, NCLX-mediated mitochondrial Ca2+ 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.

Original languageEnglish
Pages (from-to)436-441
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number1
StatePublished - 2010


  • CGP-37157
  • Mitochondrial calcium exchanger
  • Mitochondrial calcium homeostasis
  • Sodium calcium exchanger


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