Glucose-derived glutamate drives neuronal terminal differentiation in vitro.
Glutamate
Local Protein Translation in Neurons
Metabolism
Mitochondrial Pyruvate Carrier
Journal
EMBO reports
ISSN: 1469-3178
Titre abrégé: EMBO Rep
Pays: England
ID NLM: 100963049
Informations de publication
Date de publication:
19 Jan 2024
19 Jan 2024
Historique:
received:
13
07
2023
accepted:
19
12
2023
revised:
01
12
2023
medline:
20
1
2024
pubmed:
20
1
2024
entrez:
19
1
2024
Statut:
aheadofprint
Résumé
Neuronal maturation is the phase during which neurons acquire their final characteristics in terms of morphology, electrical activity, and metabolism. However, little is known about the metabolic pathways governing neuronal maturation. Here, we investigate the contribution of the main metabolic pathways, namely glucose, glutamine, and fatty acid oxidation, during the maturation of primary rat hippocampal neurons. Blunting glucose oxidation through the genetic and chemical inhibition of the mitochondrial pyruvate transporter reveals that this protein is critical for the production of glutamate, which is required for neuronal arborization, proper dendritic elongation, and spine formation. Glutamate supplementation in the early phase of differentiation restores morphological defects and synaptic function in mitochondrial pyruvate transporter-inhibited cells. Furthermore, the selective activation of metabotropic glutamate receptors restores the impairment of neuronal differentiation due to the reduced generation of glucose-derived glutamate and rescues synaptic local translation. Fatty acid oxidation does not impact neuronal maturation. Whereas glutamine metabolism is important for mitochondria, it is not for endogenous glutamate production. Our results provide insights into the role of glucose-derived glutamate as a key player in neuronal terminal differentiation.
Identifiants
pubmed: 38243137
doi: 10.1038/s44319-023-00048-8
pii: 10.1038/s44319-023-00048-8
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : EC | Horizon Europe | Excellent Science | HORIZON EUROPE Marie Sklodowska-Curie Actions (MSCA)
ID : 101072759
Organisme : Ministero dell'Università e della Ricerca (MUR)
ID : 20202THZAW
Organisme : Ministero dell'Università e della Ricerca (MUR)
ID : 2017MYJ5TH
Organisme : Ministero dell'Università e della Ricerca (MUR)
ID : 2017B9NCSX
Organisme : Ministero dell'Università e della Ricerca (MUR)
ID : 202039WMFP
Organisme : Ministero dell'Università e della Ricerca (MUR)
ID : 2017 (5C22WM)
Organisme : Fondazione Regionale per la Ricerca Biomedica (FRRB)
ID : CP 20/2018
Organisme : Fondazione Cariplo (Cariplo Foundation)
ID : 2018-0511
Organisme : Fondazione Umberto Veronesi (Umberto Veronesi Foundation)
ID : N/A
Organisme : Ministero della Salute (Italy Ministry of Health)
ID : Ricerca Corrente and "5xmille"
Informations de copyright
© 2024. The Author(s).
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