L-arginine homeostasis governs adult neural stem cell activation by modulating energy metabolism in vivo.
EMBO J
; 42(6): e112647, 2023 03 15.
Article
en En
| MEDLINE
| ID: mdl-36740997
ABSTRACT
Neurogenesis in the developing and adult brain is intimately linked to remodeling of cellular metabolism. However, it is still unclear how distinct metabolic programs and energy sources govern neural stem cell (NSC) behavior and subsequent neuronal differentiation. Here, we found that adult mice lacking the mitochondrial urea metabolism enzyme, Arginase-II (Arg-II), exhibited NSC overactivation, thereby leading to accelerated NSC pool depletion and decreased hippocampal neurogenesis over time. Mechanistically, Arg-II deficiency resulted in elevated L-arginine levels and induction of a metabolic shift from glycolysis to oxidative phosphorylation (OXPHOS) caused by impaired attachment of hexokinase-I to mitochondria. Notably, selective inhibition of OXPHOS ameliorated NSC overactivation and restored abnormal neurogenesis in Arg-II deficient mice. Therefore, Arg-II-mediated intracellular L-arginine homeostasis directly influences the metabolic fitness of neural stem cells that is essential to maintain neurogenesis with age.
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Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Células-Madre Neurales
Límite:
Animals
Idioma:
En
Revista:
EMBO J
Año:
2023
Tipo del documento:
Article
País de afiliación:
China