RT info:eu-repo/semantics/article
T1 Spatial Separation of Mitochondrial Calcium Uptake and Extrusion for Energy-Efficient Mitochondrial Calcium Signaling in the Heart
A1 Fuente Pérez, Sergio De La
AB 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.
PB cell press
YR 2018
FD 2018
LK https://uvadoc.uva.es/handle/10324/77794
UL https://uvadoc.uva.es/handle/10324/77794
LA eng
NO De La Fuente S, Lambert JP, Nichtova Z, Fernandez Sanz C, Elrod JW, Sheu SS, Csordás G. Spatial Separation of Mitochondrial Calcium Uptake and Extrusion for Energy-Efficient Mitochondrial Calcium Signaling in the Heart. Cell Rep. 2018 Sep 18;24(12):3099-3107.e4. doi: 10.1016/j.celrep.2018.08.040. PMID: 30231993; PMCID: PMC6226263.
NO Producción Científica
DS UVaDOC
RD 04-dic-2025