Cited by 107Mitochondrial Function and PathologyNeuroscience and Neuropharmacology ResearchAmino Acid Enzymes and Metabolism

Glutamate Transport Decreases Mitochondrial pH and Modulates Oxidative Metabolism in Astrocytes

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Azarias, Guillaume, Perreten, Hélène, Lengacher, Sylvain, Poburko, Damon, Demaurex, Nicolas, Magistretti, Pierre J., Chatton, Jean-Yves·2011·The Journal of Neuroscience

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.

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Crossref · 10.1523/jneurosci.4378-10.2011

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  • Astrocytes may become acidified due to proton cotransport during glutamate reuptake, which could lead to reduced mitochondrial oxygen consumption within astrocytes.

    “Astrocytes may become acidified due to proton cotransport during glutamate reuptake, which could lead to reduced mitochondrial oxygen consumption within astrocytes66.”

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Authors
Azarias, G., Perreten, H., Lengacher, S., Poburko, D., Demaurex, N., Magistretti, P. J., & Chatton, J.-Y.
Affiliations
  • University of Lausanne (CH)
  • École Polytechnique Fédérale de Lausanne (CH)
  • University of Geneva (CH)
Corresponding author
Chatton, Jean-Yves
Venue
The Journal of Neuroscience
Published
2011-03-09
Volume
31
Issue
10
Pages
3550-3559
ISSN
  • 0270-6474 (ISSN-L)
  • 1529-2401
OpenAlex
W2084578352
Cited by
107
References
48
Citations by year
2026: 3 · 2025: 4 · 2024: 4 · 2023: 2 · 2022: 4 · 2021: 4 · 2020: 5 · 2019: 9 · 2018: 14 · 2017: 7 · 2016: 6 · 2015: 9 · 2014: 11 · 2013: 8 · 2012: 12
FWCI
4.67
Type
journal article
Language
en
Open access
Locations
  • Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Archive ouverte UNIGE (University of Geneva) (publishedVersion, other-oa)
  • IRIS (submittedVersion)
  • Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion)
  • Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
  • SERVAL (Université de Lausanne) (submittedVersion, other-oa)
  • Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
Funders
  • National Science Foundation
  • Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (119827, 3100A0)
  • Università di Bologna
  • Università degli Studi di Ferrara
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
Keywords
glutamate uptake, astrocytes, mitochondrial pH, oxidative metabolism, intracellular sodium, excitatory neurotransmission, reactive oxygen species, astrocyte energy metabolism, calcium signaling
MeSH terms
Analysis of Variance, Animals, Astrocytes, Biological Transport, Cells, Cultured, Cerebral Cortex, Energy Metabolism, Hydrogen-Ion Concentration, Mitochondria, Neurons, Oxygen, Glutamic Acid, Amino Acid Transport System X-AG, Mice

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