Mitochondrial pyruvate metabolism regulates the activation of quiescent adult neural stem cells.

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Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_E7DE603E4491
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Mitochondrial pyruvate metabolism regulates the activation of quiescent adult neural stem cells.
Journal
Science advances
Author(s)
Petrelli F., Scandella V., Montessuit S., Zamboni N., Martinou J.C., Knobloch M.
ISSN
2375-2548 (Electronic)
ISSN-L
2375-2548
Publication state
Published
Issued date
03/2023
Peer-reviewed
Oui
Volume
9
Number
9
Pages
eadd5220
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
Cellular metabolism is important for adult neural stem/progenitor cell (NSPC) behavior. However, its role in the transition from quiescence to proliferation is not fully understood. We here show that the mitochondrial pyruvate carrier (MPC) plays a crucial and unexpected part in this process. MPC transports pyruvate into mitochondria, linking cytosolic glycolysis to mitochondrial tricarboxylic acid cycle and oxidative phosphorylation. Despite its metabolic key function, the role of MPC in NSPCs has not been addressed. We show that quiescent NSPCs have an active mitochondrial metabolism and express high levels of MPC. Pharmacological MPC inhibition increases aspartate and triggers NSPC activation. Furthermore, genetic Mpc1 ablation in vitro and in vivo also activates NSPCs, which differentiate into mature neurons, leading to overall increased hippocampal neurogenesis in adult and aged mice. These findings highlight the importance of metabolism for NSPC regulation and identify an important pathway through which mitochondrial pyruvate import controls NSPC quiescence and activation.
Keywords
Animals, Mice, Neurogenesis, Neurons, Biological Transport, Neural Stem Cells, Mitochondria, Monocarboxylic Acid Transporters
Pubmed
Open Access
Yes
Create date
09/03/2023 16:16
Last modification date
14/03/2023 7:50
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