Role of AGC1/aralar in the metabolic synergies between neuron and glia

• Aralar, the mitochondrial aspartate–glutamate carrier, is expressed mainly in neurons.
• Aralar–MAS pathway is essential for normal glucose oxidative metabolism in neurons.
• Neuron to astrocyte aspartate flux provides NH4 for de novo glutamate synthesis.
• Glutamate protection in photoreceptors relies on cytosolic redox power.
• Photoreceptor Asp and Lact compensate missing MAS and PKM2 in Müller cells.

Brain energetic requirements are elevated due to the high cost of impulse transmission and information storage, and are met mainly by glucose oxidation. The energy needs are closely matched by metabolic regulation, which requires the close cooperation of neurons and astrocytes and involves highly regulated fluxes of metabolites between cells. The metabolism in each type of cell is determined in part by its proteomic profile, which has been regarded as complementary. This review will consider the cellular distribution of the mitochondrial aspartate–glutamate carrier, aralar/AGC1/SLC25A12, and its role in the synergic metabolism between neurons and astrocytes.