Deacetylation of PGC-1α by SIRT1: importance for skeletal muscle function and exercise-induced mitochondrial biogenesis
Abstract
Activation of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α)-mediated transcription is important for both the determination of mitochondrial content and the induction of mitochondrial biogenesis in skeletal muscle. SIRT1 (silent mating type information regulator 2 homolog 1) deactetylation is proposed as a potential activator of PGC-1α transcriptional activity. The current review examines the importance of SIRT1 deacetylation of PGC-1α in skeletal muscle. Models of SIRT1 overexpression and pharmacological activation are examined, but changes in SIRT1 expression and deacetylase activity following acute and chronic contractile activity will be emphasized. In addition, potential mechanisms of SIRT1 activation in skeletal muscle will be examined. The importance of the PGC-1α acetyltransferase GCN5 will also be briefly discussed. The current evidence supports the contribution of SIRT1 deacetylation of PGC-1α to exercise-induced mitochondrial biogenesis. Further research examining exercise-mediated activation of SIRT1 and the role of GCN5 in regulating PGC-1α transcriptional activity in skeletal muscle is required.
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SIRT1 is a key regulator of skeletal muscle biological function, including muscle atrophy, glycolipid metabolism, muscle cytokine secretion, and mitochondrial function.
“SIRT1 is a key regulator of skeletal muscle biological function, such as muscle atrophy, glycolipid metabolism, muscle cytokine secretion, and mitochondrial function.16”
From GLP-1RA Liraglutide and Semaglutide Improves Obesity-Induced Muscle Atrophy via SIRT1 Pathway (2023) · cites this paper as [16]
SIRT1 has been implicated in turnover of defective mitochondria by mitophagy, in addition to its role in promoting mitochondrial biogenesis.
“In apparent contrast with its role in promoting mitochondrial biogenesis through peroxisome proliferator-activated receptor-γ co-activator 1α deacetylation19–21, SIRT1 has also been implicated in turnover of defective mitochondria by mitophagy22,23.”
From NAD+ metabolism and its roles in cellular processes during ageing (2021) · cites this paper as [21]
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References 87 · Cited by 171
- Authors
- Gurd, B. J.
- Affiliations
- Queen's University (CA)
- Corresponding author
- Gurd, Brendon J.
- ORCID
- Gurd, Brendon J.
- Venue
- Applied Physiology, Nutrition, and Metabolism
- Publisher
- Canadian Science Publishing
- Published
- 2011-10
- Volume
- 36
- Issue
- 5
- Pages
- 589-597
- ISSN
- 1715-5312 (ISSN-L)
- 1715-5320
- OpenAlex
- W2099082614
- Cited by
- 171
- References
- 87
- Citations by year
- 2026: 11 · 2025: 21 · 2024: 12 · 2023: 17 · 2022: 11 · 2021: 16 · 2020: 11 · 2019: 8 · 2018: 5 · 2017: 10 · 2016: 11 · 2015: 7 · 2014: 9 · 2013: 12 · 2012: 10
- FWCI
- 0.81
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Applied Physiology, Nutrition, and Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- PGC-1α, SIRT1, protein deacetylation, skeletal muscle, physical activity, mitochondrial biogenesis, GCN5, acetyltransferase, transcriptional coactivator, SIRT1 activation, contractile activity
- MeSH terms
- Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, p300-CBP-Associated Factor, Acetylation, Animals, Heat-Shock Proteins, Humans, Mitochondria, Muscle, Motor Activity, Protein Processing, Post-Translational, Transcription Factors, Exercise, Transcriptional Activation, Muscle, Skeletal, p300-CBP Transcription Factors, Sirtuin 1
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