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Published in Journal of Cell Science - 27 Jul 2018

Francesca Pala, Daniela Di Girolamo, Sébastien Mella, Siham Yennek, Laurent Chatre, Miria Ricchetti, Shahragim Tajbakhsh

Link to Pubmed [PMID] – 30054310

Link to HAL – hal-02420316

Link to DOI – 10.1242/jcs.212977

Journal of Cell Science, 2018, 131 (14), pp.jcs212977. ⟨10.1242/jcs.212977⟩

During growth, homeostasis and regeneration, stem cells are exposed to different energy demands. Here, we characterise the metabolic pathways that mediate the commitment and differentiation of mouse skeletal muscle stem cells, and how their modulation can influence the cell state. We show that quiescent satellite stem cells have low energetic demands and perturbed oxidative phosphorylation during ageing, which is also the case for cells from post-mortem tissues. We show also that myogenic fetal cells have distinct metabolic requirements compared to those proliferating during regeneration, with the former displaying a low respiration demand relying mostly on glycolysis. Furthermore, we show distinct requirements for peroxisomal and mitochondrial fatty acid oxidation (FAO) in myogenic cells. Compromising peroxisomal but not mitochondrial FAO promotes early differentiation of myogenic cells. Acute muscle injury and pharmacological block of peroxisomal and mitochondrial FAO expose differential requirements for these organelles during muscle regeneration. Taken together, these observations indicate that changes in myogenic cell state lead to significant alterations in metabolic requirements. In addition, perturbing specific metabolic pathways impacts on myogenic cell fates and the regeneration process.