Mitochondrial Dysfunction Launches Dexamethasone-Induced Skeletal Muscle Atrophy via AMPK/FOXO3 Signaling
Abstract
Muscle atrophy occurs in several pathologic conditions such as diabetes and chronic obstructive pulmonary disease (COPD), as well as after long-term clinical administration of synthesized glucocorticoid, where increased circulating glucocorticoid accounts for the pathogenesis of muscle atrophy. Others and we previously reported mitochondrial dysfunction in muscle atrophy-related conditions and that mitochondria-targeting nutrients efficiently prevent kinds of muscle atrophy. However, whether and how mitochondrial dysfunction involves glucocorticoid-induced muscle atrophy remains unclear. Therefore, in the present study, we measured mitochondrial function in dexamethasone-induced muscle atrophy in vivo and in vitro, and we found that mitochondrial respiration was compromised on the 3rd day following after dexamethasone administration, earlier than the increases of MuRF1 and Fbx32, and dexamethasone-induced loss of mitochondrial components and key mitochondrial dynamics proteins. Furthermore, dexamethasone treatment caused intracellular ATP deprivation and robust AMPK activation, which further activated the FOXO3/Atrogenes pathway. By directly impairing mitochondrial respiration, FCCP leads to similar readouts in C2C12 myotubes as dexamethasone does. On the contrary, resveratrol, a mitochondrial nutrient, efficiently reversed dexamethasone-induced mitochondrial dysfunction and muscle atrophy in both C2C12 myotubes and mice, by improving mitochondrial function and blocking AMPK/…
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Mitochondrial respiration can be affected by external factors such as glucocorticoid use.
“Of note, mitochondrial respiration can be affected by external factors, such as glucocorticoid use [105]”
From Main Pathogenic Mechanisms and Recent Advances in COPD Peripheral Skeletal Muscle Wasting (2023) · cites this paper as [105]
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- Authors
- Liu, J., Peng, Y., Wang, X., Fan, Y., Qin, C., Shi, L., Tang, Y., Cao, K., Li, H., Long, J., & Liu, J.
- Affiliations
- Tianjin University of Sport (CN)
- Corresponding author
- Long, Jiangang
- Liu, Jiankang
- ORCID
- Venue
- Molecular Pharmaceutics
- Publisher
- American Chemical Society (ACS)
- Published
- 2015-12-17
- Volume
- 13
- Issue
- 1
- Pages
- 73-84
- ISSN
- 1543-8384 (ISSN-L)
- 1543-8392
- OpenAlex
- W2176504547
- Cited by
- 133
- References
- 56
- Citations by year
- 2026: 14 · 2025: 12 · 2024: 17 · 2023: 10 · 2022: 17 · 2021: 14 · 2020: 17 · 2019: 10 · 2018: 6 · 2017: 7 · 2016: 9
- FWCI
- 3.19
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular Pharmaceutics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- State Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center (SMFA15K01)
- Ministry of Education of the People's Republic of China (8143008, 8143101)
- Ministry of Science and Technology of the People's Republic of China (2015CB553602, 2015CB856302)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Keywords
- skeletal muscle atrophy, dexamethasone, glucocorticoid-induced muscle atrophy, mitochondrial dysfunction, mitochondrial respiration, atrogenes, MuRF1, mitochondrial dynamics, ATP depletion, resveratrol, C2C12 myotubes
- MeSH terms
- Resveratrol, Animals, Cell Differentiation, Cell Line, Dexamethasone, Male, Mice, Inbred C57BL, Muscular Atrophy, Stilbenes, Signal Transduction, Muscle, Skeletal, Mice
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