Developmental changes in the Ca2+-regulated mitochondrial aspartate-glutamate carrier aralar1 in brain and prominent expression in the spinal cord

• Published in: Brain research. Developmental brain research Vol. 143; no. 1; pp. 33 - 46
• Main Authors: Ramos, Milagros, del Arco, Araceli, Pardo, Beatriz, Martínez-Serrano, Alberto, Martínez-Morales, Juan Ramón, Kobayashi, Keiko, Yasuda, Tomotsugu, Bogónez, Elena, Bovolenta, Paola, Saheki, Takeyori, Satrústegui, Jorgina
• Format: Journal Article
• Language: English
• Published: Netherlands 12.06.2003
• Subjects: Amino Acid Transport Systems, Acidic - metabolism; Animals; Antiporters - metabolism; Blotting, Southern; Blotting, Western - methods; Brain - drug effects; Brain - embryology; Brain - metabolism; Calcium - metabolism; Calcium-Binding Proteins - metabolism; Cell Line; Cells, Cultured; DNA, Mitochondrial - biosynthesis; Embryo, Mammalian; Gene Expression Regulation, Developmental; Glutamic Acid - pharmacology; In Situ Hybridization; Lactic Acid - pharmacology; Malates - pharmacology; Membrane Transport Proteins - metabolism; Mice; Mitochondria - metabolism; Mitochondrial Membrane Transport Proteins; Mitochondrial Proteins - metabolism; Neuroglia - metabolism; Neurons - metabolism; Organic Anion Transporters - metabolism; Phosphoric Monoester Hydrolases - pharmacology; Protein Isoforms - metabolism; Proton-Translocating ATPases - metabolism; Rats; Rats, Wistar; Spinal Cord - drug effects; Spinal Cord - embryology; Spinal Cord - metabolism; Stem Cells - enzymology; Stem Cells - metabolism; Succinic Acid - pharmacology; Tetrazolium Salts - pharmacology; Thiazoles - pharmacology; Time Factors; Tissue Distribution
• ISSN: 0165-3806
• DOI: 10.1016/s0165-3806(03)00097-x

Aralar1 and citrin are two isoforms of the mitochondrial carrier of aspartate-glutamate (AGC), a calcium regulated carrier, which is important in the malate-aspartate NADH shuttle. The expression and cell distribution of aralar1 and citrin in brain cells has been studied during development in vitro and in vivo. Aralar1 is the only isoform expressed in neurons and its levels undergo a marked increase during in vitro maturation, which is higher than the increase in mitochondrial DNA in the same time window. The enrichment in aralar1 per mitochondria during neuronal maturation is associated with a prominent rise in the function of the malate-aspartate NADH shuttle. Paradoxically, during in vivo development of rat or mouse brain there is very little postnatal increase in total aralar1 levels per mitochondria. This is explained by the fact that astrocytes develop postnatally, have aralar1 levels much lower than neurons, and their increase masks that of aralar1. Aralar1 mRNA and protein are widely expressed throughout neuron-rich areas in adult mouse CNS with clear enrichments in sets of neuronal nuclei in the brainstem and, particularly, in the ventral horn of the spinal cord. These aralar1-rich neurons represent a subset of the cytochrome oxidase-rich neurons in the same areas. The presence of aralar1 could reflect a tonic activity of these neurons, which is met by the combination of high malate-aspartate NADH shuttle and respiratory chain activities.