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Role of PGC-1α Signaling in Skeletal Muscle Health and Disease
Open accessAbstract
This paper reviews the current understanding of the molecular basis of the peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α)-mediated pathway and discusses the role of PGC-1α in skeletal muscle atrophy caused by immobilization. PGC-1α is the master transcription regulator that stimulates mitochondrial biogenesis, by upregulating nuclear respiratory factors (NRF-1, 2) and mitochondrial transcription factor A (Tfam), which leads to increased mitochondrial DNA replication and gene transcription. PGC-1α also regulates cellular oxidant-antioxidant homeostasis by stimulating the gene expression of superoxide dismutase-2 (SOD2), catalase, glutathione peroxidase 1 (GPx1), and uncoupling protein (UCP). Recent reports from muscle-specific PGC-1α overexpression underline the importance of PGC-1α in atrophied skeletal muscle, demonstrate enhancement of the PGC-1α mitochondrial biogenic pathway, and reduced oxidative damage. Thus, PGC-1α appears to play a protective role against atrophy-linked skeletal muscle deterioration.
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“Through deacetylation, AMPK upregulates the expression of PGC-1α via the SIRT1 signaling pathway which in turn modulates FoxO transcriptional activity by repressing the expression of key atrogenes such as atrogin-1 and muscle RING-finger protein-1 (MuRF1), thereby preventing proteasome-mediated muscle protein degradation while simultaneously enhancing mitochondrial biogenesis, antioxidant defense,”
From Exercise-Induced Muscle–Fat Crosstalk: Molecular Mediators and Their Pharmacological Modulation for the Maintenance of Metabolic Flexibility in Aging (2025) · cites this paper as [103]
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In the citing paper
“In addition, PPARGC1A inhibits the expression of multiple pro‐inflammatory mediators, including TNF‐α and IL‐6, and regulates antioxidant defense mechanisms (Kang & Li Ji, 2012), both of which in turn can activate autophagy.”
From Autophagy gene expression in skeletal muscle of older individuals is associated with physical performance, muscle volume and mitochondrial function in the study of muscle, mobility and aging ( SOMMA ) (2024) · cites this paper as Kang & Li Ji, 2012
In the citing paper
“ApN may also induce Ca2+ influx, thereby activating CaMKKβ, which leads to increased expression of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), a key player in mitochondrial function and biogenesis [42,43].”
From Adiponectin and Its Mimics on Skeletal Muscle: Insulin Sensitizers, Fat Burners, Exercise Mimickers, Muscling Pills … or Everything Together? (2020) · cites this paper as [43]
In the citing paper
“Second, activation of PGC-1α enhances the expression of several oxidative-stress detoxification enzymes and molecules involved in fatty-acid oxidation [43,51].”
From Adiponectin and Its Mimics on Skeletal Muscle: Insulin Sensitizers, Fat Burners, Exercise Mimickers, Muscling Pills … or Everything Together? (2020) · cites this paper as [43]
In the citing paper
“Eventually, as mentioned earlier, PGC-1α is also a regulator of cellular oxidant–antioxidant homeostasis by stimulating gene expression of several antioxidant enzymes such as superoxide dismutase-2, catalase, and glutathione peroxidase [43].”
From Adiponectin and Its Mimics on Skeletal Muscle: Insulin Sensitizers, Fat Burners, Exercise Mimickers, Muscling Pills … or Everything Together? (2020) · cites this paper as [43]
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1 retracted
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A Cold-Inducible Coactivator of Nuclear Receptors Linked to Adaptive Thermogenesis
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Transcriptional co-activator PGC-1α drives the formation of slow-twitch muscle fibres
Lin, J., Wu, H., Tarr, P. T., Zhang, C.-Y., Wu, Z., Boss, O., Michael, L. F., Puigserver, P., Isotani, E., Olson, E. N., et al. (2002) · Nature · doi:10.1038/nature00904 · Cited by 2,546
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Lin, J., Handschin, C., & Spiegelman, B. M. (2005) · Cell Metabolism · doi:10.1016/j.cmet.2005.05.004 · Cited by 2,130
Puigserver, P., & Spiegelman, B. M. (2003) · Endocrine Reviews · doi:10.1210/er.2002-0012 · Cited by 2,076
Research works printed but not linked: 3
- 10.1016/S0092-8674(00)80611-X · DOI · Paper page
- 10.1038/nature00904 · DOI · Paper page
- Kang C., 2012, PGC‐1α enhances skeletal muscle recovery from disuse atrophy, Med. Sci. Sports Exer., 44, S501
Cited by
Sorted by citations
Role of ROS and RNS Sources in Physiological and Pathological Conditions
Meo, S. D., Reed, T. T., Venditti, P., & Víctor, V. M. (2016) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2016/1245049 · Cited by 1,712
Mitochondrial Dysfunction and Oxidative Stress in Alzheimer’s Disease
Misrani, A., Tabassum, S., & Yang, L. (2021) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2021.617588 · Cited by 654
PGC-1 α , Inflammation, and Oxidative Stress: An Integrative View in Metabolism
Rius‐Pérez, S., Torres-Cuevas, I., Millán, I., Ortega, Á., & Pérez, S. (2020) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2020/1452696 · Cited by 671
PGC-1α Is a Master Regulator of Mitochondrial Lifecycle and ROS Stress Response
Abu Shelbayeh, O., Arroum, T., Morris, S., & Busch, K. B. (2023) · Antioxidants · doi:10.3390/antiox12051075 · Cited by 552
Mechanisms for fiber-type specificity of skeletal muscle atrophy
Wang, Y., & Pessin, J. E. (2013) · Current Opinion in Clinical Nutrition & Metabolic Care · doi:10.1097/mco.0b013e328360272d · Cited by 432
Metadata
- Authors
- Kang, C., & Li Ji, L.
- Affiliations
- University of Minnesota (US)
- ORCID
- Kang, Chounghun
- Venue
- Annals of the New York Academy of Sciences
- Publisher
- Wiley
- Published
- 2012-10
- Volume
- 1271
- Issue
- 1
- Pages
- 110-117
- ISSN
- 0077-8923 (ISSN-L)
- 1749-6632
- PMC
- PMC3499658
- OpenAlex
- W1524273338
- Cited by
- 291
- References
- 60
- Citations by year
- 2026: 24 · 2025: 32 · 2024: 35 · 2023: 31 · 2022: 20 · 2021: 30 · 2020: 30 · 2019: 17 · 2018: 18 · 2017: 12 · 2016: 9 · 2015: 15 · 2014: 11 · 2013: 7
- FWCI
- 0.96
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Annals of the New York Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Keywords
- PGC-1α, skeletal muscle atrophy, immobilization, mitochondrial biogenesis, nuclear respiratory factors, TFAM, oxidative stress, antioxidant enzymes, manganese superoxide dismutase, uncoupling proteins, muscle health
- MeSH terms
- Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Aging, Animals, Heat-Shock Proteins, Humans, Muscular Atrophy, Musculoskeletal Diseases, Oxidoreductases, Transcription Factors, Signal Transduction, Exercise, Gene Expression Regulation, Enzymologic, Muscle, Skeletal, Mitochondrial Turnover
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