| First Author | De La Fuente S | Year | 2018 |
| Journal | Cell Rep | Volume | 24 |
| Issue | 12 | Pages | 3099-3107.e4 |
| PubMed ID | 30231993 | Mgi Jnum | J:270797 |
| Mgi Id | MGI:6278734 | Doi | 10.1016/j.celrep.2018.08.040 |
| Citation | De La Fuente S, et al. (2018) Spatial Separation of Mitochondrial Calcium Uptake and Extrusion for Energy-Efficient Mitochondrial Calcium Signaling in the Heart. Cell Rep 24(12):3099-3107.e4 |
| abstractText | Mitochondrial Ca(2+) elevations enhance ATP production, but uptake must be balanced by efflux to avoid overload. Uptake is mediated by the mitochondrial Ca(2+) uniporter channel complex (MCUC), and extrusion is controlled largely by the Na(+)/Ca(2+) exchanger (NCLX), both driven electrogenically by the inner membrane potential (DeltaPsim). MCUC forms hotspots at the cardiac mitochondria-junctional SR (jSR) association to locally receive Ca(2+) 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 Ca(2+) 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 Ca(2+) expends more DeltaPsim. Thus, cardiac mitochondrial Ca(2+) uptake and extrusion are reciprocally polarized, likely to optimize the energy efficiency of local calcium signaling in the beating heart. |
