Spatial Separation of Mitochondrial Calcium Uptake and Extrusion for Energy-Efficient Mitochondrial Calcium Signaling in the Heart
| Autor: | John Elrod, Gyorgy Csordas, Jonathan Lambert, Sergio De la Fuente, Celia Fernández Sanz, Celia Fernandez-Sanz, Zuzana Nichtova |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine Matrix (biology) Mitochondria Heart Article General Biochemistry Genetics and Molecular Biology Cell Line Rats Sprague-Dawley Mice 03 medical and health sciences 0302 clinical medicine medicine Animals Inner membrane Mitochondrial calcium uptake Calcium Signaling Uniporter lcsh:QH301-705.5 Calcium signaling Membrane Potential Mitochondrial Chemistry Myocardium Sodium Cardiac muscle Rats Cell biology Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure lcsh:Biology (General) Calcium Extrusion Efflux 030217 neurology & neurosurgery |
| Zdroj: | Cell Reports, Vol 24, Iss 12, Pp 3099-3107.e4 (2018) Cell reports |
| ISSN: | 2211-1247 |
| Popis: | SUMMARY 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 jSRassociated 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. In Brief Calcium signals control mitochondrial fuel generation. De La Fuente et al. report that in heart mitochondria, calcium uptake and extrusion are spatially separated; the most calcium-exposed area is an uptake hotspot, but it lacks extrusion to optimize signaling efficiency and minimize the energy expense of controlling mitochondrial function by calcium. Graphical Abstract |
| Databáze: | OpenAIRE |
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