In:
Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 107, No. 1 ( 2010-01-05), p. 436-441
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.
Type of Medium:
Online Resource
ISSN:
0027-8424
,
1091-6490
DOI:
10.1073/pnas.0908099107
Language:
English
Publisher:
Proceedings of the National Academy of Sciences
Publication Date:
2010
detail.hit.zdb_id:
209104-5
detail.hit.zdb_id:
1461794-8
SSG:
11
SSG:
12
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