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

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

AMPKα1-LDH pathway regulates muscle stem cell self-renewal by controlling metabolic homeostasis. / Theret, Marine; Gsaier, Linda; Schaffer, Bethany; Juban, Gaëtan; Ben Larbi, Sabrina; Weiss-Gayet, Michèle; Bultot, Laurent; Collodet, Caterina; Foretz, Marc; Desplanches, Dominique; Sanz, Pascual; Zang, Zizhao; Yang, Lin; Vial, Guillaume; Viollet, Benoit; Sakamoto, Kei; Brunet, Anne; Chazaud, Bénédicte; Mounier, Rémi.

In: EMBO Journal, Vol. 36, No. 13, 03.07.2017, p. 1946-1962.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Theret, M, Gsaier, L, Schaffer, B, Juban, G, Ben Larbi, S, Weiss-Gayet, M, Bultot, L, Collodet, C, Foretz, M, Desplanches, D, Sanz, P, Zang, Z, Yang, L, Vial, G, Viollet, B, Sakamoto, K, Brunet, A, Chazaud, B & Mounier, R 2017, 'AMPKα1-LDH pathway regulates muscle stem cell self-renewal by controlling metabolic homeostasis', EMBO Journal, vol. 36, no. 13, pp. 1946-1962. https://doi.org/10.15252/embj.201695273

APA

Theret, M., Gsaier, L., Schaffer, B., Juban, G., Ben Larbi, S., Weiss-Gayet, M., Bultot, L., Collodet, C., Foretz, M., Desplanches, D., Sanz, P., Zang, Z., Yang, L., Vial, G., Viollet, B., Sakamoto, K., Brunet, A., Chazaud, B., & Mounier, R. (2017). AMPKα1-LDH pathway regulates muscle stem cell self-renewal by controlling metabolic homeostasis. EMBO Journal, 36(13), 1946-1962. https://doi.org/10.15252/embj.201695273

Vancouver

Theret M, Gsaier L, Schaffer B, Juban G, Ben Larbi S, Weiss-Gayet M et al. AMPKα1-LDH pathway regulates muscle stem cell self-renewal by controlling metabolic homeostasis. EMBO Journal. 2017 Jul 3;36(13):1946-1962. https://doi.org/10.15252/embj.201695273

Author

Theret, Marine ; Gsaier, Linda ; Schaffer, Bethany ; Juban, Gaëtan ; Ben Larbi, Sabrina ; Weiss-Gayet, Michèle ; Bultot, Laurent ; Collodet, Caterina ; Foretz, Marc ; Desplanches, Dominique ; Sanz, Pascual ; Zang, Zizhao ; Yang, Lin ; Vial, Guillaume ; Viollet, Benoit ; Sakamoto, Kei ; Brunet, Anne ; Chazaud, Bénédicte ; Mounier, Rémi. / AMPKα1-LDH pathway regulates muscle stem cell self-renewal by controlling metabolic homeostasis. In: EMBO Journal. 2017 ; Vol. 36, No. 13. pp. 1946-1962.

Bibtex

@article{4911ad19483e4be9b5c609e161d2e00d,
title = "AMPKα1-LDH pathway regulates muscle stem cell self-renewal by controlling metabolic homeostasis",
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.",
keywords = "glycolysis, metabolic shift, skeletal muscle regeneration, stem cell fate",
author = "Marine Theret and Linda Gsaier and Bethany Schaffer and Ga{\"e}tan Juban and {Ben Larbi}, Sabrina and Mich{\`e}le Weiss-Gayet and Laurent Bultot and Caterina Collodet and Marc Foretz and Dominique Desplanches and Pascual Sanz and Zizhao Zang and Lin Yang and Guillaume Vial and Benoit Viollet and Kei Sakamoto and Anne Brunet and B{\'e}n{\'e}dicte Chazaud and R{\'e}mi Mounier",
year = "2017",
month = jul,
day = "3",
doi = "10.15252/embj.201695273",
language = "English",
volume = "36",
pages = "1946--1962",
journal = "E M B O Journal",
issn = "0261-4189",
publisher = "Wiley-Blackwell",
number = "13",

}

RIS

TY - JOUR

T1 - AMPKα1-LDH pathway regulates muscle stem cell self-renewal by controlling metabolic homeostasis

AU - Theret, Marine

AU - Gsaier, Linda

AU - Schaffer, Bethany

AU - Juban, Gaëtan

AU - Ben Larbi, Sabrina

AU - Weiss-Gayet, Michèle

AU - Bultot, Laurent

AU - Collodet, Caterina

AU - Foretz, Marc

AU - Desplanches, Dominique

AU - Sanz, Pascual

AU - Zang, Zizhao

AU - Yang, Lin

AU - Vial, Guillaume

AU - Viollet, Benoit

AU - Sakamoto, Kei

AU - Brunet, Anne

AU - Chazaud, Bénédicte

AU - Mounier, Rémi

PY - 2017/7/3

Y1 - 2017/7/3

N2 - 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.

AB - 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.

KW - glycolysis

KW - metabolic shift

KW - skeletal muscle regeneration

KW - stem cell fate

U2 - 10.15252/embj.201695273

DO - 10.15252/embj.201695273

M3 - Journal article

C2 - 28515121

AN - SCOPUS:85019269977

VL - 36

SP - 1946

EP - 1962

JO - E M B O Journal

JF - E M B O Journal

SN - 0261-4189

IS - 13

ER -

ID: 238739193