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

Details

Serval ID
serval:BIB_3F2EBAE91AD9
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Mitochondrial biogenesis in developing astrocytes regulates astrocyte maturation and synapse formation.
Journal
Cell reports
Author(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)
Publication state
Published
Issued date
13/04/2021
Peer-reviewed
Oui
Volume
35
Number
2
Pages
108952
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
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.
Keywords
PGC-1α, astrocyte, mGluR5, mitochondria
Pubmed
Web of science
Open Access
Yes
Create date
27/04/2021 14:54
Last modification date
22/05/2021 6:34
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