Mitochondrial maintenance via autophagy contributes to functional skeletal muscle regeneration and remodeling
Abstract
The primary objective of this study was to determine whether alterations in mitochondria affect recovery of skeletal muscle strength and mitochondrial enzyme activity following myotoxic injury. 3-Methyladenine (3-MA) was administered daily (15 mg/kg) to blunt autophagy, and the creatine analog guanidionpropionic acid (β-GPA) was administered daily (1% in chow) to enhance oxidative capacity. Male C57BL/6 mice were randomly assigned to nontreatment (Con, n = 6), 3-MA-treated ( n = 6), and β-GPA-treated ( n = 8) groups for 10 wk. Mice were euthanized at 14 days after myotoxic injury for assessment of mitochondrial remodeling during regeneration and its association with the recovery of muscle strength. Expression of several autophagy-related proteins, e.g., phosphorylated Ulk1 (∼2- to 4-fold, P < 0.049) was greater in injured than uninjured muscles, indicating a relationship between muscle regeneration/remodeling and autophagy. By 14 days postinjury, recovery of muscle strength (18% less, P = 0.03) and mitochondrial enzyme (e.g., citrate synthase) activity (22% less, P = 0.049) were significantly lower in 3-MA-treated than Con mice, suggesting that the autophagy process plays an important role during muscle regeneration. In contrast, muscle regeneration was nearly complete in β-GPA-treated mice, i.e., muscle strength recovered to 93% of baseline vs. 78% for Con mice. Remarkably, 14 days allowed sufficient time for a near-complete recovery of mitochondrial function in β-GPA-treated mice (e.g., no difference in citrate synthase activity between injured and uninjured, P = 0.49), indicating a robust mitochondrial remodeling process during muscle regeneration. In conclusion, autophagy is likely activated following muscle injury and appears to play an important role in functional muscle regeneration.
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Autophagy inhibition with 3-methyladenine blunts recovery in mice after myotoxic injury.
“since autophagy inhibition with 3-methyladenine blunts recovery in mice after myotoxic injury [475].”
From Autophagy and ALS: mechanistic insights and therapeutic implications (2022) · cites this paper as [475]
Autophagy appears to be required for muscle regeneration.
“Autophagy appears to be required for muscle regeneration, since autophagy inhibition with 3-methyladenine blunts recovery in mice after myotoxic injury [475].”
From Autophagy and ALS: mechanistic insights and therapeutic implications (2022) · cites this paper as [475]
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Autophagy and ALS: mechanistic insights and therapeutic implications
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“Skeletal muscle Activates [475] Activates [482] RUNX1 [474]”
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- Authors
- Nichenko, A. S., Southern, W. M., Atuan, M., Luan, J., Peissig, K. B., Foltz, S. J., Beedle, A. M., Warren, G. L., & Call, J. A.
- Affiliations
- University of Georgia (US)
- Department of Pharmaceutical and Biomedical Sciences, University of Georgia, Athens, Georgia; and
- Georgia State University (US)
- Corresponding author
- Call, Jarrod A.
- ORCID
- Venue
- American Journal of Physiology-Cell Physiology
- Publisher
- American Physiological Society
- Published
- 2016-08-01
- Volume
- 311
- Issue
- 2
- Pages
- C190-C200
- ISSN
- 0363-6143 (ISSN-L)
- 1522-1563
- OpenAlex
- W2415429505
- Cited by
- 80
- References
- 36
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 11 · 2023: 11 · 2022: 9 · 2021: 11 · 2020: 3 · 2019: 12 · 2018: 8 · 2017: 8 · 2016: 1
- FWCI
- 5.03
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Physiology-Cell Physiology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Keywords
- autophagy, mitochondrial maintenance, skeletal muscle regeneration, muscle remodeling, muscle strength recovery, 3-methyladenine, citrate synthase, mitochondrial enzyme activity, ULK1 phosphorylation, oxidative capacity
- MeSH terms
- Adenine, Animals, Autophagy, Male, Mice, Inbred C57BL, Mitochondria, Muscle, Muscular Diseases, Regeneration, Wound Healing, Muscle, Skeletal, Recovery of Function, Mice, Muscle Strength
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