TY - JOUR T1 - Glutamate Transport Decreases Mitochondrial pH and Modulates Oxidative Metabolism in Astrocytes JF - The Journal of Neuroscience JO - J. Neurosci. SP - 3550 LP - 3559 DO - 10.1523/JNEUROSCI.4378-10.2011 VL - 31 IS - 10 AU - Guillaume Azarias AU - Hélène Perreten AU - Sylvain Lengacher AU - Damon Poburko AU - Nicolas Demaurex AU - Pierre J. Magistretti AU - Jean-Yves Chatton Y1 - 2011/03/09 UR - http://www.jneurosci.org/content/31/10/3550.abstract N2 - During synaptic activity, the clearance of neuronally released glutamate leads to an intracellular sodium concentration increase in astrocytes that is associated with significant metabolic cost. The proximity of mitochondria at glutamate uptake sites in astrocytes raises the question of the ability of mitochondria to respond to these energy demands. We used dynamic fluorescence imaging to investigate the impact of glutamatergic transmission on mitochondria in intact astrocytes. Neuronal release of glutamate induced an intracellular acidification in astrocytes, via glutamate transporters, that spread over the mitochondrial matrix. The glutamate-induced mitochondrial matrix acidification exceeded cytosolic acidification and abrogated cytosol-to-mitochondrial matrix pH gradient. By decoupling glutamate uptake from cellular acidification, we found that glutamate induced a pH-mediated decrease in mitochondrial metabolism that surpasses the Ca2+-mediated stimulatory effects. These findings suggest a model in which excitatory neurotransmission dynamically regulates astrocyte energy metabolism by limiting the contribution of mitochondria to the metabolic response, thereby increasing the local oxygen availability and preventing excessive mitochondrial reactive oxygen species production. ER -