Mitochondrial biogenesis in developing astrocytes regulates astrocyte maturation and synapse formation.

Détails

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Etat: Public
Version: de l'auteur⸱e
Licence: CC BY-NC-ND 4.0
ID Serval
serval:BIB_3F2EBAE91AD9
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Mitochondrial biogenesis in developing astrocytes regulates astrocyte maturation and synapse formation.
Périodique
Cell reports
Auteur⸱e⸱s
Zehnder T., Petrelli F., Romanos J., De Oliveira Figueiredo E.C., Lewis T.L., Déglon N., Polleux F., Santello M., Bezzi P.
ISSN
2211-1247 (Electronic)
Statut éditorial
Publié
Date de publication
13/04/2021
Peer-reviewed
Oui
Volume
35
Numéro
2
Pages
108952
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Résumé
The mechanisms controlling the post-natal maturation of astrocytes play a crucial role in ensuring correct synaptogenesis. We show that mitochondrial biogenesis in developing astrocytes is necessary for coordinating post-natal astrocyte maturation and synaptogenesis. The astrocytic mitochondrial biogenesis depends on the transient upregulation of metabolic regulator peroxisome proliferator-activated receptor gamma (PPARγ) co-activator 1α (PGC-1α), which is controlled by metabotropic glutamate receptor 5 (mGluR5). At tissue level, the loss or downregulation of astrocytic PGC-1α sustains astrocyte proliferation, dampens astrocyte morphogenesis, and impairs the formation and function of neighboring synapses, whereas its genetic re-expression is sufficient to restore the mitochondria compartment and correct astroglial and synaptic defects. Our findings show that the developmental enhancement of mitochondrial biogenesis in astrocytes is a critical mechanism controlling astrocyte maturation and supporting synaptogenesis, thus suggesting that astrocytic mitochondria may be a therapeutic target in the case of neurodevelopmental and psychiatric disorders characterized by impaired synaptogenesis.
Mots-clé
PGC-1α, astrocyte, mGluR5, mitochondria
Pubmed
Web of science
Open Access
Oui
Création de la notice
27/04/2021 13:54
Dernière modification de la notice
26/07/2022 5:37
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