| First Author | Theret M | Year | 2017 |
| Journal | EMBO J | Volume | 36 |
| Issue | 13 | Pages | 1946-1962 |
| PubMed ID | 28515121 | Mgi Jnum | J:243577 |
| Mgi Id | MGI:5909156 | Doi | 10.15252/embj.201695273 |
| Citation | Theret M, et al. (2017) AMPKalpha1-LDH pathway regulates muscle stem cell self-renewal by controlling metabolic homeostasis. EMBO J 36(13):1946-1962 |
| abstractText | 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. AMPKalpha1-/- MuSCs displayed a high self-renewal rate, which impairs muscle regeneration. AMPKalpha1-/- MuSCs showed a Warburg-like switch of their metabolism to higher glycolysis. We identified lactate dehydrogenase (LDH) as a new functional target of AMPKalpha1. LDH, which is a non-limiting enzyme of glycolysis in differentiated cells, was tightly regulated in stem cells. In functional experiments, LDH overexpression phenocopied AMPKalpha1-/- phenotype, that is shifted MuSC metabolism toward glycolysis triggering their return to quiescence, while inhibition of LDH activity rescued AMPKalpha1-/- MuSC self-renewal. Finally, providing specific nutrients (galactose/glucose) to MuSCs directly controlled their fate through the AMPKalpha1/LDH pathway, emphasizing the importance of metabolism in stem cell fate. |
