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Spatial Separation of Mitochondrial Calcium Uptake and Extrusion for Energy-Efficient Mitochondrial Calcium Signaling in the Heart
de la Fuente, Sergio Nichtova, Zuzana Fernandez Sanz, Celia Sheu, Shey-Shing Csordas, Gyorgy
de la Fuente, Sergio
Nichtova, Zuzana
Fernandez Sanz, Celia
Sheu, Shey-Shing
Csordas, Gyorgy
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Journal article
Date
2018-09-18
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Center for Translational Medicine (Temple University)
Department
Cardiovascular Sciences
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https://doi.org/10.1016/j.celrep.2018.08.040
Abstract
Mitochondrial Ca2+ elevations enhance ATP production, but uptake must be balanced by efflux to avoid overload. Uptake is mediated by the mitochondrial Ca2+ uniporter channel complex (MCUC), and extrusion is controlled largely by the Na+/Ca2+ exchanger (NCLX), both driven electrogenically by the inner membrane potential (ΔΨm). MCUC forms hotspots at the cardiac mitochondria-junctional SR (jSR) association to locally receive Ca2+ signals; however, the distribution of NCLX is unknown. Our fractionation-based assays reveal that extensively jSR-associated mitochondrial segments contain a minor portion of NCLX and lack Na+-dependent Ca2+ extrusion. This pattern is retained upon in vivo NCLX overexpression, suggesting extensive targeting to non-jSR-associated submitochondrial domains and functional relevance. In cells with non-polarized MCUC distribution, upon NCLX overexpression the same given increase in matrix Ca2+ expends more ΔΨm. Thus, cardiac mitochondrial Ca2+ uptake and extrusion are reciprocally polarized, likely to optimize the energy efficiency of local calcium signaling in the beating heart.
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Cell Press
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Cell Reports, Vol. 24, Iss. 12
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