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. Synopsis Tang and Rando report induction of autophagy by the nutrient sensor SIRT1 as crucial energy provider for efficient proliferation/differentiation in quiescent muscle satellite cells in vivo . Muscle stem cells require autophagy to surmount a bioenergetic hurdle to break quiescence to enter an activated state. Bioenergetic demands accompanying muscle stem cell activation induces autophagic flux. These bioenergetic demands are signaled through SIRT1 to activate autophagy by interaction with ATG7 and through the AMPK pathway. Graphical Abstract Tang and Rando report induction of autophagy by the nutrient sensor SIRT1 as crucial energy provider for efficient proliferation/differentiation in quiescent muscle satellite cells in vivo .