神经发生
生物
神经干细胞
精氨酸酶
己糖激酶
线粒体
细胞生物学
精氨酸
氧化磷酸化
干细胞
平衡
糖酵解
海马结构
新陈代谢
生物化学
内分泌学
氨基酸
作者
Mingyue Xu,Yifeng Guo,Min Wang,Xing Luo,Xiaoxia Shen,Zhimin Li,Lei Wang,Weixiang Guo
标识
DOI:10.15252/embj.2022112647
摘要
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.
科研通智能强力驱动
Strongly Powered by AbleSci AI