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FoxO3 coordinates metabolic pathways to maintain redox balance in neural stem cells
Author(s) -
Yeo Hyeonju,
Lyssiotis Costas A,
Zhang Yuqing,
Ying Haoqiang,
Asara John M,
Cantley Lewis C,
Paik JiHye
Publication year - 2013
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2013.186
Subject(s) - biology , foxo3 , neural stem cell , stem cell , microbiology and biotechnology , redox , balance (ability) , signal transduction , neuroscience , protein kinase b , materials science , metallurgy
Forkhead Box O (FoxO) transcription factors act in adult stem cells to preserve their regenerative potential. Previously, we reported that FoxO maintains the long‐term proliferative capacity of n eural stem/ p rogenitor c ells (NPCs), and that this occurs, in part, through the maintenance of redox homeostasis. Herein, we demonstrate that among the FoxO3‐regulated genes in NPCs are a host of enzymes in central carbon metabolism that act to combat reactive oxygen species (ROS) by directing the flow of glucose and glutamine carbon into defined metabolic pathways. Characterization of the metabolic circuit observed upon loss of FoxO3 revealed a drop in glutaminolysis and filling of the tricarboxylic acid (TCA) cycle. Additionally, we found that glucose uptake, glucose metabolism and oxidative pentose phosphate pathway activity were similarly repressed in the absence of FoxO3. Finally, we demonstrate that impaired glucose and glutamine metabolism compromises the proliferative potential of NPCs and that this is exacerbated following FoxO3 loss. Collectively, our findings show that a FoxO3‐dependent metabolic programme supports redox balance and the neurogenic potential of NPCs.