AMPKα1-LDH pathway regulates muscle stem cell self-renewal by controlling metabolic homeostasis

The EMBO Journal
Marine ThéretRémi Mounier

Abstract

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. AMPKα1-/- MuSCs displayed a high self-renewal rate, which impairs muscle regeneration. AMPKα1-/- MuSCs showed a Warburg-like switch of their metabolism to higher glycolysis. We identified lactate dehydrogenase (LDH) as a new functional target of AMPKα1. LDH, which is a non-limiting enzyme of glycolysis in differentiated cells, was tightly regulated in stem cells. In functional experiments, LDH overexpression phenocopied AMPKα1-/- phenotype, that is shifted MuSC metabolism toward glycolysis triggering their return to quiescence, while inhibition of LDH activity rescued AMPKα1-/- MuSC self-renewal. Finally, providing specific nutrients (galactose/glucose) to MuSCs directly controlled their fate through the AMPKα1/LDH pathway, emphasizing the importance of metabolism in stem cell fate.

References

May 1, 1991·British Journal of Cancer·A NishikawaH Mori
Feb 1, 1969·Archives of Biochemistry and Biophysics·P A Srere, G C Brooks
Aug 4, 1999·Proceedings of the National Academy of Sciences of the United States of America·M TiainenT P Mäkelä
Sep 11, 1999·Nucleic Acids Research·P MiniouJ Melki
Jan 4, 2003·The Journal of Clinical Investigation·Benoit ViolletSophie Vaulont
Jul 28, 2004·The Journal of Cell Biology·Peter S ZammitJonathan R Beauchamp
Apr 21, 2005·Proceedings of the National Academy of Sciences of the United States of America·Arvind RamanathanStuart L Schreiber
Dec 8, 2005·American Journal of Physiology. Endocrinology and Metabolism·Kei SakamotoLuc Bertrand
May 9, 2007·The Journal of Experimental Medicine·Ludovic ArnoldBénédicte Chazaud
Jun 2, 2007·Cell·Shihuan KuangMichael A Rudnicki
Jan 19, 2008·Nature Reviews. Genetics·Keith W Orford, David T Scadden
Feb 21, 2008·Nature Reviews. Molecular Cell Biology·M Celeste Simon, Brian Keith
Feb 25, 2009·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Rémi MounierBenoit Viollet
Nov 20, 2009·Developmental Cell·Christine A GriffinGrace K Pavlath
Jan 19, 2010·Nature Cell Biology·Aaron W B JoeFabio M V Rossi
Feb 11, 2010·Cell Stem Cell·Justin Voog, D Leanne Jones
May 13, 2010·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Louise LantierBenoit Viollet
Aug 5, 2010·Cell Stem Cell·Ahmed MohyeldinAlfredo Quiñones-Hinojosa
Nov 27, 2010·Journal of Hepatology·Guillaume VialXavier M Leverve
Dec 3, 2010·Nature·Sushma GurumurthyNabeel Bardeesy
Mar 16, 2011·The Journal of Cell Biology·Damien LaporteIsabelle Sagot
Jul 30, 2011·Cell Cycle·Rémi MounierBenoit Viollet
Feb 22, 2012·Journal of Cell Science·Yusuke OnoShin'ichi Takeda
Mar 23, 2012·Nature Reviews. Molecular Cell Biology·D Grahame HardieSimon A Hawley
May 9, 2012·Cell Stem Cell·Massimiliano CerlettiAmy J Wagers
Jun 14, 2012·Nature Communications·Mathilde LatilFabrice Chrétien
Jun 19, 2012·Cell Stem Cell·Jane E Visvader, Geoffrey J Lindeman

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Citations

Dec 16, 2017·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Rasmus KjøbstedLouise Lantier
Apr 27, 2018·Current Opinion in Clinical Nutrition and Metabolic Care·James G Ryall, Gordon S Lynch
Mar 6, 2019·International Journal of Cancer. Journal International Du Cancer·Han-Wei TanRegina Cheuk-Lam Lo
Apr 24, 2019·Molecular & Cellular Proteomics : MCP·Tommy Weiss-SadanGalia Blum
May 8, 2019·Tissue Engineering. Part a·Jessica BouvièreBénédicte Chazaud
Feb 7, 2018·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Athan G DialVladimir Ljubicic
Jun 6, 2019·Epigenetics & Chromatin·Ting ZhangGang Li
Oct 14, 2018·International Journal of Molecular Sciences·David M Thomson
Jan 11, 2020·Frontiers in Cell and Developmental Biology·Gunjan Purohit, Jyotsna Dhawan
Feb 6, 2020·The Journal of Clinical Investigation·Simon McArthurRémi Mounier
Feb 18, 2020·Future Medicinal Chemistry·Mark R WoodfordMehdi Mollapour
Jan 11, 2018·Cell Cycle·Marine TheretRémi Mounier
Oct 12, 2019·Cell Death & Disease·Yuantong LiuZhenzhong Li
Dec 28, 2018·Npj Regenerative Medicine·Brendan Evano, Shahragim Tajbakhsh
Dec 29, 2020·Frontiers in Physiology·Minas NalbandianMasaki Takeda
Dec 15, 2020·World Journal of Stem Cells·Meng LuoJiao-Jiao Zhou
Jul 1, 2019·Molecular & Cellular Proteomics : MCP·Tommy Weiss-SadanGalia Blum
Jan 31, 2021·Nature Communications·F Relaix Taglietti
Mar 7, 2021·Trends in Cell Biology·Sara AncelJerome N Feige
Mar 19, 2021·Frontiers in Cell and Developmental Biology·Yasuro FuruichiYasuko Manabe
Mar 21, 2021·The Journal of Investigative Dermatology·Elizabeth D CraneJustin D Crane
Mar 24, 2021·Proceedings of the National Academy of Sciences of the United States of America·Shaopu ZhouZhenguo Wu
Apr 4, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Jung Ho HanKi-Tae Ha
Apr 13, 2021·Journal of Neuromuscular Diseases·Sabrina Ben LarbiBénédicte Chazaud
May 21, 2020·Cell Metabolism·C Hai LyJames G Ryall
Aug 14, 2021·Stem Cell Reports·Benjamin A YangCarlos A Aguilar
Sep 3, 2021·Journal of Cell Science·Marielle SaclierGaëtan Juban

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