Metabolic control of adult neural stem cell self-renewal by the mitochondrial protease YME1L.
Adult Stem Cells
/ cytology
Animals
Cell Proliferation
Cell Self Renewal
Citric Acid Cycle
Fatty Acids
/ metabolism
Gene Deletion
Metalloendopeptidases
/ deficiency
Mice, Inbred C57BL
Mice, Knockout
Mitochondria
/ enzymology
Neural Stem Cells
/ cytology
Nucleotides
/ metabolism
Oxidation-Reduction
Proteolysis
Proteome
/ metabolism
OMA1
YME1L
adult neurogenesis
metabolic rewiring
mitochondria
mitochondrial dynamics
mitochondrial proteome
neural stem cells
proliferation
self-renewal
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
15 02 2022
15 02 2022
Historique:
received:
21
08
2021
revised:
29
11
2021
accepted:
20
01
2022
entrez:
16
2
2022
pubmed:
17
2
2022
medline:
3
3
2022
Statut:
ppublish
Résumé
The transition between quiescence and activation in neural stem and progenitor cells (NSPCs) is coupled with reversible changes in energy metabolism with key implications for lifelong NSPC self-renewal and neurogenesis. How this metabolic plasticity is ensured between NSPC activity states is unclear. We find that a state-specific rewiring of the mitochondrial proteome by the i-AAA peptidase YME1L is required to preserve NSPC self-renewal. YME1L controls the abundance of numerous mitochondrial substrates in quiescent NSPCs, and its deletion activates a differentiation program characterized by broad metabolic changes causing the irreversible shift away from a fatty-acid-oxidation-dependent state. Conditional Yme1l deletion in adult NSPCs in vivo results in defective self-renewal and premature differentiation, ultimately leading to NSPC pool depletion. Our results disclose an important role for YME1L in coordinating the switch between metabolic states of NSPCs and suggest that NSPC fate is regulated by compartmentalized changes in protein network dynamics.
Identifiants
pubmed: 35172139
pii: S2211-1247(22)00091-2
doi: 10.1016/j.celrep.2022.110370
pii:
doi:
Substances chimiques
Fatty Acids
0
Nucleotides
0
Proteome
0
Metalloendopeptidases
EC 3.4.24.-
YME1L protein, mouse
EC 3.4.24.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
110370Informations de copyright
Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests.