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Science China Life Sciences

, Volume 58, Issue 1, pp 59–65

First Online: 10 January 2015Received: 15 August 2014Accepted: 17 October 2014DOI: 10.1007-s11427-014-4789-9

Cite this article as: Nita, L.I., Hershfinkel, M. & Sekler, I. Sci. China Life Sci. 2015 58: 59. doi:10.1007-s11427-014-4789-9


Powered by the mitochondrial membrane potential, Ca permeates the mitochondria via a Ca channel termed Ca uniporter and is pumped out by a Na-Ca exchanger, both of which are located on the inner mitochondrial membrane. Mitochondrial Ca transients are critical for metabolic activity and regulating global Ca responses. On the other hand, failure to control mitochondrial Ca is a hallmark of ischemic and neurodegenerative diseases. Despite their importance, identifying the uniporter and exchanger remains elusive and their inhibitors are non-specific. This review will focus on the mitochondrial exchanger, initially describing how it was molecularly identified and linked to a novel member of the Na-Ca exchanger superfamily termed NCLX. Molecular control of NCLX expression provides a selective tool to determine its physiological role in a variety of cell types. In lymphocytes, NCLX is essential for refilling the endoplasmic reticulum Ca stores required for antigendependent signaling. Communication of NCLX with the store-operated channel in astroglia controls Ca influx and thereby neuro-transmitter release and cell proliferation. The refilling of the Ca stores in the sarcoplasmic reticulum, which is controlled by NCLX, determines the frequency of action potential and Ca transients in cardiomyocytes. NCLX is emerging as a hub for integrating glucose-dependent Na and Ca signaling in pancreatic β cells, and the specific molecular control of NCLX expression resolved the controversy regarding its role in neurons and β cells. Future studies on an NCLX knockdown mouse model and identification of human NCLX mutations are expected to determine the role of mitochondrial Ca efflux in organ activity and whether NCLX inactivation is linked to ischemic and-or neurodegenerative syndromes. Structure-function analysis and protein analysis will identify the NCLX mode of regulation and its partners in the inner membrane of the mitochondria.

KeywordsNCLX MCU mitochondrial Ca signaling Na-Ca exchanger Na signaling This article is published with open access at

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Autor: Lulia I. Nita - Michal Hershfinkel - Israel Sekler


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