期刊
EMBO JOURNAL
卷 36, 期 13, 页码 1946-1962出版社
WILEY
DOI: 10.15252/embj.201695273
关键词
glycolysis; metabolic shift; skeletal muscle regeneration; stem cell fate
资金
- European Commission integrated project [LSHM-CT-2004-005272]
- Framework Programme FP7 Endostem [241440]
- Association Francaise contre les Myopathies
- Ligue Nationale Contre le Cancer
- Societe Francaise de Myologie
Control of stem cell fate to either enter terminal differentiation versus returning to quiescence (self-renewal) is crucial for tissue repair. Here, we showed that AMP-activated protein kinase (AMPK), the master metabolic regulator of the cell, controls muscle stem cell (MuSC) self-renewal. AMPK alpha 1(-/-) MuSCs displayed a high self-renewal rate, which impairs muscle regeneration. AMPK alpha 1(-/-) MuSCs showed a Warburg-like switch of their metabolism to higher glycolysis. We identified lactate dehydrogenase (LDH) as a new functional target of AMPK alpha 1. LDH, which is a non-limiting enzyme of glycolysis in differentiated cells, was tightly regulated in stem cells. In functional experiments, LDH overexpression phenocopied AMPK alpha 1(-/-) phenotype, that is shifted MuSC metabolism toward glycolysis triggering their return to quiescence, while inhibition of LDH activity rescued AMPK alpha 1(-/-) MuSC self-renewal. Finally, providing specific nutrients (galactose/glucose) to MuSCs directly controlled their fate through the AMPK alpha 1/LDH pathway, emphasizing the importance of metabolism in stem cell fate.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据