TableEdit

Palty, R, Silverman, WF, Hershfinkel, M, Caporale, T, Sensi, SL, Parnis, J, Nolte, C, Fishman, D, Shoshan-Barmatz, V, Herrmann, S, Khananshvili, D and Sekler, I (2010) NCLX is an essential component of mitochondrial Na+/Ca2+ exchange. Proc. Natl. Acad. Sci. U.S.A. 107:436-41

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.

PubMed PMC2806722 Online version:10.1073/pnas.0908099107

Animals; Brain/cytology; Brain/metabolism; Calcium/metabolism; Clonazepam/analogs & derivatives; Clonazepam/metabolism; Homeostasis; Humans; Mice; Mitochondria/metabolism; Mitochondria/ultrastructure; Mitochondrial Membranes/metabolism; Mitochondrial Membranes/ultrastructure; Myocardium/cytology; Myocardium/metabolism; Rats; Sodium/metabolism; Sodium-Calcium Exchanger/antagonists & inhibitors; Sodium-Calcium Exchanger/genetics; Sodium-Calcium Exchanger/metabolism; Thiazepines/metabolism