RRC ID 31377
Author Tang AH, Rando TA.
Title Induction of autophagy supports the bioenergetic demands of quiescent muscle stem cell activation.
Journal EMBO J
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.
Volume 33(23)
Pages 2782-97
Published 2014-12-1
DOI 10.15252/embj.201488278
PII embj.201488278
PMID 25316028
PMC PMC4282556
MeSH Adenosine Triphosphate / metabolism Animals Autophagy / physiology* Cell Differentiation / physiology* Deoxyuridine / analogs & derivatives Energy Metabolism / physiology* Fluorescent Antibody Technique Gene Expression Regulation / physiology* Green Fluorescent Proteins / metabolism Immunoprecipitation Mice Mice, Transgenic Microtubule-Associated Proteins / metabolism Muscle, Skeletal / cytology* Reverse Transcriptase Polymerase Chain Reaction Sirtuin 1 / metabolism* Stem Cells / physiology*
IF 9.889
Times Cited 122
WOS Category BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY
Resource
Mice RBRC00806 RBRC02975