en
Scientific article
Open access
English

Glutamate transport decreases mitochondrial pH and modulates oxidative metabolism in astrocytes

Published inThe Journal of neuroscience, vol. 31, no. 10, p. 3550-3559
Publication date2011
Abstract

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 Ca(2+)-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.

Keywords
  • Amino Acid Transport System X-AG/metabolism
  • Analysis of Variance
  • Animals
  • Astrocytes/metabolism
  • Biological Transport
  • Cells, Cultured
  • Cerebral Cortex/metabolism
  • Energy Metabolism
  • Glutamic Acid/metabolism
  • Hydrogen-Ion Concentration
  • Mice
  • Mitochondria/metabolism
  • Neurons/metabolism
  • Oxygen/metabolism
Citation (ISO format)
AZARIAS, Guillaume et al. Glutamate transport decreases mitochondrial pH and modulates oxidative metabolism in astrocytes. In: The Journal of neuroscience, 2011, vol. 31, n° 10, p. 3550–3559. doi: 10.1523/JNEUROSCI.4378-10.2011
Main files (1)
Article (Published version)
accessLevelPublic
Identifiers
ISSN of the journal0270-6474
535views
576downloads

Technical informations

Creation06/04/2012 7:58:00 PM
First validation06/04/2012 7:58:00 PM
Update time03/14/2023 5:37:03 PM
Status update03/14/2023 5:37:03 PM
Last indexation05/02/2024 12:33:20 PM
All rights reserved by Archive ouverte UNIGE and the University of GenevaunigeBlack