title: NCLX: the mitochondrial sodium calcium exchanger.
abstract: The free Ca(2+) concentration within the mitochondrial matrix ([Ca(2+)]m) regulates the rate of ATP production and other [Ca(2+)]m sensitive processes. It is set by the balance between total Ca(2+) influx (through the mitochondrial Ca(2+) uniporter (MCU) and any other influx pathways) and the total Ca(2+) efflux (by the mitochondrial Na(+)/Ca(2+) exchanger and any other efflux pathways). Here we review and analyze the experimental evidence reported over the past 40years which suggest that in the heart and many other mammalian tissues a putative Na(+)/Ca(2+) exchanger is the major pathway for Ca(2+) efflux from the mitochondrial matrix. We discuss those reports with respect to a recent discovery that the protein product of the human FLJ22233 gene mediates such Na(+)/Ca(2+) exchange across the mitochondrial inner membrane. Among its many functional similarities to other Na(+)/Ca(2+) exchanger proteins is a unique feature: it efficiently mediates Li(+)/Ca(2+) exchange (as well as Na(+)/Ca(2+) exchange) and was therefore named NCLX. The discovery of NCLX provides both the identity of a novel protein and new molecular means of studying various unresolved quantitative aspects of mitochondrial Ca(2+) movement out of the matrix. Quantitative and qualitative features of NCLX are discussed as is the controversy regarding the stoichiometry of the NCLX Na(+)/Ca(2+) exchange, the electrogenicity of NCLX, the [Na(+)]i dependency of NCLX and the magnitude of NCLX Ca(2+) efflux. Metabolic features attributable to NCLX and the physiological implication of the Ca(2+) efflux rate via NCLX during systole and diastole are also briefly discussed.
authors.affiliation: Center for Biomedical Engineering and Technology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
authors.forename: Liron
authors.initials: L
authors.lastname: Boyman
authors.forename: George S B
authors.initials: GS
authors.lastname: Williams
authors.forename: Daniel
authors.initials: D
authors.lastname: Khananshvili
authors.forename: Israel
authors.initials: I
authors.lastname: Sekler
authors.forename: W J
authors.initials: WJ
authors.lastname: Lederer
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D019295:Computational Biology; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D019831:Sodium-Calcium Exchanger / Q000378:metabolism*
chemical_list: D019831:Sodium-Calcium Exchanger; D002118:Calcium
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