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

Departamento de Biología Molecular, Centro de Biología Molecular Severo Ochoa, Universidad Autónoma de Madrid, 28049 Madrid, Spain.
Developmental Brain Research (Impact Factor: 1.78). 07/2003; 143(1):33-46. DOI: 10.1016/S0165-3806(03)00097-X
Source: PubMed


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.

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    • "Nonetheless, the absence of aralar from glia is in agreement with several results obtained by biochemical and inmunolabeling classical procedures. Previous work of immunohistochemical profiling by confocal microscopy found aralar in brain with a clear if not exclusive preference for neuronal populations (Berkich et al., 2007; Ramos et al., 2003). This distribution is re-enforced by biochemical data that support the idea of lower oxidative glucose metabolism in astrocytes compared with neurons (Belanger et al., 2011). "
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    • "And third, in situ generation of mitochondrial Glu avoids another problem faced by synaptic cytosolic Glu: its import into astrocytic mitochondria. It has been shown that brain astrocytes do not express the main aspartate-glutamate carrier (Aralar/AGC1) (Ramos et al., 2003; Berckich et al., 2007); therefore, exogenous Glu must enter into astrocytes uniquely by the Glu/ hydroxyl carrier. However, results obtained from KO mice for Aralar underscored the importance of this carrier for Glu transport in brain and skeletal muscle mitochondria (Jalil et al., 2005), and further evidences indicate that no other Glu carrier can substitute for Aralar in those tissues (Satr ustegui et al., 2007 and references therein). "
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