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Mitochondrial sodium/calcium exchanger NCLX regulates glycolysis in astrocytes, impacting on cognitive performance
Cabral-Costa, João Victor Vicente-Gutiérrez, Carlos Agulla, Jesús Lapresa, Rebeca Almeida, Ángeles Bolaños, Juan P. Kowaltowski, Alicia J.
Cabral-Costa, João Victor
Vicente-Gutiérrez, Carlos
Agulla, Jesús
Lapresa, Rebeca
Almeida, Ángeles
Bolaños, Juan P.
Kowaltowski, Alicia J.
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Journal article
Date
2023-01-09
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Cardiovascular Sciences
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https://doi.org/10.1111/jnc.15745
Abstract
Intracellular Ca2+ concentrations are strictly controlled by plasma membrane transporters, the endoplasmic reticulum, and mitochondria, in which Ca2+ uptake is mediated by the mitochondrial calcium uniporter complex (MCUc), while efflux occurs mainly through the mitochondrial Na+/Ca2+ exchanger (NCLX). RNAseq database repository searches led us to identify the Nclx transcript as highly enriched in astrocytes when compared with neurons. To assess the role of NCLX in mouse primary culture astrocytes, we inhibited its function both pharmacologically or genetically. This resulted in re-shaping of cytosolic Ca2+ signaling and a metabolic shift that increased glycolytic flux and lactate secretion in a Ca2+-dependent manner. Interestingly, in vivo genetic deletion of NCLX in hippocampal astrocytes improved cognitive performance in behavioral tasks, whereas hippocampal neuron-specific deletion of NCLX impaired cognitive performance. These results unveil a role for NCLX as a novel modulator of astrocytic glucose metabolism, impacting on cognition.
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Cabral-Costa, J. V., Vicente-Gutiérrez, C., Agulla, J., Lapresa, R., Elrod, J. W., Almeida, Á., Bolaños, J. P., & Kowaltowski, A. J. (2023). Mitochondrial sodium/calcium exchanger NCLX regulates glycolysis in astrocytes, impacting on cognitive performance. Journal of Neurochemistry, 165, 521–535. https://doi.org/10.1111/jnc.15745
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Wiley
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Journal of Neurochemistry (JNC), Vol. 165, Iss. 4
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