title: Induction of autophagy supports the bioenergetic demands of quiescent muscle stem cell activation.
abstract: 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.
authors.affiliation: Paul F. Glenn Center for the Biology of Aging, Stanford University School of Medicine, Stanford, CA, USA Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Ann H
authors.initials: AH
authors.lastname: Tang
authors.affiliation: Paul F. Glenn Center for the Biology of Aging, Stanford University School of Medicine, Stanford, CA, USA Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA Neurology Service and Rehabilitation Research and Developmental Center of Excellence, Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, USA rando@stanford.edu.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Rando
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001343:Autophagy / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology*; D003857:Deoxyuridine / Q000031:analogs & derivatives; D004734:Energy Metabolism / Q000502:physiology*; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation / Q000502:physiology*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D047468:Immunoprecipitation; D051379:Mice; D008822:Mice, Transgenic; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000166:cytology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D056564:Sirtuin 1 / Q000378:metabolism*; D013234:Stem Cells / Q000502:physiology*
chemical_list: C480860:Map1lc3b protein, mouse; D008869:Microtubule-Associated Proteins; D049452:Green Fluorescent Proteins; D000255:Adenosine Triphosphate; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1; C031086:5-ethynyl-2'-deoxyuridine; D003857:Deoxyuridine
keywords: SIRT1; activation; autophagy; quiescence; satellite cell