RGD Reference Report - NCLX is an essential component of mitochondrial Na+/Ca2+ exchange. - Rat Genome Database

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

Authors: Palty, R  Silverman, WF  Hershfinkel, M  Caporale, T  Sensi, SL  Parnis, J  Nolte, C  Fishman, D  Shoshan-Barmatz, V  Herrmann, S  Khananshvili, D  Sekler, I 
Citation: Palty R, etal., Proc Natl Acad Sci U S A. 2010 Jan 5;107(1):436-41. doi: 10.1073/pnas.0908099107. Epub 2009 Dec 15.
RGD ID: 9685493
Pubmed: PMID:20018762   (View Abstract at PubMed)
PMCID: PMC2806722   (View Article at PubMed Central)
DOI: DOI:10.1073/pnas.0908099107   (Journal Full-text)

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.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

Cellular Component
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
mitochondrial crista located_inIDA 9685493PMID:20018762BHF-UCL 
mitochondrion located_inIDA 9685493PMID:20018762BHF-UCL 

Molecular Function

Objects Annotated

Genes (Rattus norvegicus)
Slc8b1  (solute carrier family 8 member B1)


Additional Information