Mitochondrial biogenesis in developing astrocytes regulates astrocyte maturation and synapse formation.
Details
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License: CC BY-NC-ND 4.0
UNIL restricted access
State: Public
Version: author
License: CC BY-NC-ND 4.0
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
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
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 13:54
Last modification date
26/07/2022 5:37