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Induction of autophagy supports the bioenergetic demands of quiescent muscle stem cell activation
Open accessAbstract
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 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. 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.
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“SIRT1 was also found to promote autophagy in quiescent MuSCs, and in this case, a loss of SIRT1 leads to a delay in MuSC activation out of quiescence — similar to what is observed in aged muscles109.”
From Ageing and rejuvenation of tissue stem cells and their niches (2023) · cites this paper as [109]
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“Autophagy is also required for activation out of quiescence109, and defects in autophagic activity with ageing lead to increased cell death during activation110.”
From Ageing and rejuvenation of tissue stem cells and their niches (2023) · cites this paper as [109]
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Metadata
- Authors
- Tang, A. H., & Rando, T. A.
- Affiliations
- Stanford Medicine (US)
- VA Palo Alto Health Care System (US)
- Corresponding author
- Rando, Thomas A
- ORCID
- Rando, Thomas A
- Venue
- The EMBO Journal
- Published
- 2014-10-14
- Volume
- 33
- Issue
- 23
- Pages
- 2782-2797
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC4282556
- OpenAlex
- W2082121028
- Cited by
- 294
- References
- 97
- Citations by year
- 2026: 13 · 2025: 24 · 2024: 26 · 2023: 19 · 2022: 30 · 2021: 26 · 2020: 28 · 2019: 26 · 2018: 28 · 2017: 34 · 2016: 19 · 2015: 20 · 2014: 1
- FWCI
- 10.12
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- public-domain
- www.springer.com/tdm (tdm)
- www.springer.com/tdm (vor)
- Locations
- The EMBO Journal (publishedVersion, public-domain)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Glenn Foundation for Medical Research
- NIH (R01 AG23806, R01 AG047820, P01 AG036695)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- autophagy, muscle stem cells, satellite cells, stem cell quiescence, stem cell activation, SIRT1, pyruvate, bioenergetics, ATP levels, nutrient sensing, proteostasis, muscle regeneration
- MeSH terms
- Adenosine Triphosphate, Animals, Autophagy, Cell Differentiation, Deoxyuridine, Energy Metabolism, Fluorescent Antibody Technique, Gene Expression Regulation, Mice, Transgenic, Microtubule-Associated Proteins, Stem Cells, Muscle, Skeletal, Reverse Transcriptase Polymerase Chain Reaction, Immunoprecipitation, Green Fluorescent Proteins, Mice, Sirtuin 1
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