Mitochondrial sodium/calcium exchanger NCLX regulates glycolysis in astrocytes, impacting on cognitive performance
Year: 2022
Type: article
Abstract: Intracellular Ca 2+ concentrations are strictly controlled by plasma membrane transporters, the endoplasmic reticulum, and mitochondria, in which Ca 2+ uptake is mediated by the mitochondrial calcium uniporter complex (MCUc), while efflux occurs mainly through the mitochondrial Na + /Ca 2+ exchanger (NCLX). RNAseq database repository searches led us to identify the Nclx transcript as highly enriched in astrocytes when compared to 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 Ca 2+ signaling and a metabolic shift that increased glycolytic flux and lactate secretion in a Ca 2+ -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.
Source: Journal of Neurochemistry
DOI: 10.1111/jnc.15745
Institutions: Consejo Superior de Investigaciones Científicas, Universidade de São Paulo, Universidad de Salamanca, Instituto de Biología Funcional y Genómica, Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red, Instituto de Investigación Biomédica de Salamanca, Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable, Temple University
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $4,700
Funders: European Commission, Fundação de Amparo à Pesquisa do Estado de São Paulo, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Conselho Nacional de Desenvolvimento Científico e Tecnológico, Junta de Castilla y León, Instituto de Salud Carlos III, Agencia Estatal de Investigación, National Institute of Neurological Disorders and Stroke, NextGenerationEU
Awards: G1171198284, G1175115578, G1374164983, G176523928, G2148579211, G2262748287, G237172224, G2382844429, G2601397997, Mitochondrial ion transporters as sensors and regulators in energy metabolism, G2672435700, G2741106897, G2822033100, G295657101, G2972037462, G2978736194, G300979063, G3480869486, G353854674, G3681454997, G3768165868, G3793187625, G4042783231, G4220107723, G425668148, G471324499, G4728539003, G5080475149, G5195188938, G5309765835, G5362556050, Mitochondria and metabolism in neurodegeneration, G5960408532, G6154769615, G6810256320, G7084143925, G7330179772, G8130184278, Función específica de las especies reactivas de oxígeno en la reparación cerebral y su impacto en el pronóstico de ictus, Redoxome - Redox Processes in Biomedicine, G8434310470, G863151887, G867133708, G8684520763, G8696694383, G8911861759, Mitochondria and metabolism in neurodegeneration
OpenAlex ID: W4312114720