Induction of autophagy supports the bioenergetic demands of quiescent muscle stem cell activation.
The exit of a stem cell out of quiescence into an activated state is characterized by major metabolic changes associated with increased biosynthesis of proteins and macromolecules. The regulation of this transition is poorly understood. Using muscle stem cells, or satellite cells (SCs), we found that autophagy, which catabolizes intracellular contents to maintain proteostasis and to produce energy during nutrient deprivation, was induced during SC activation. Inhibition of autophagy suppressed the increase in ATP levels and delayed SC activation, both of which could be partially rescued by exogenous pyruvate as an energy source, suggesting that autophagy may provide nutrients necessary to meet bioenergetic demands during this critical transition from quiescence to activation. We found that SIRT1, a known nutrient sensor, regulates autophagic flux in SC progeny. A deficiency of SIRT1 led to a delay in SC activation that could also be partially rescued by exogenous pyruvate. These studies suggest that autophagy, regulated by SIRT1, may play an important role during SC activation to meet the high bioenergetic demands of the activation process.
['Tang|Ann H|AH|', 'Rando|Thomas A|TA|']
D000255:Adenosine Triphosphate D000818:Animals D001343:Autophagy D002454:Cell Differentiation D003857:Deoxyuridine D004734:Energy Metabolism D005455:Fluorescent Antibody Technique D005786:Gene Expression Regulation D049452:Green Fluorescent Proteins D047468:Immunoprecipitation D051379:Mice D008822:Mice, Transgenic D008869:Microtubule-Associated Proteins D018482:Muscle, Skeletal D020133:Reverse Transcriptase Polymerase Chain Reaction D056564:Sirtuin 1 D013234:Stem Cells
autophagy activation quiescence satellite cell SIRT1