The DOI matches its Crossref record; 45 of the 45 references it cites were found in a registry or an index.
Autophagy is required for exercise training‐induced skeletal muscle adaptation and improvement of physical performance
Open accessAbstract
Pathological and physiological stimuli, including acute exercise, activate autophagy; however, it is unknown whether exercise training alters basal levels of autophagy and whether autophagy is required for skeletal muscle adaptation to training. We observed greater autophagy flux (i.e., a combination of increased LC3‐II/LC3‐I ratio and LC3‐II levels and reduced p62 protein content indicating a higher rate of initiation and resolution of autophagic events), autophagy protein expression (i.e., Atg6/Beclin1, Atg7, and Atg8/LC3) and mitophagy protein Bnip3 expression in tonic, oxidative muscle compared to muscles of either mixed fiber types or of predominant glycolytic fibers in mice. Long‐term voluntary running (4 wk) resulted in increased basal autophagy flux and expression of autophagy proteins and Bnip3 in parallel to mitochondrial biogenesis in plantaris muscle with mixed fiber types. Conversely, exercise training promoted autophagy protein expression with no significant increases of autophagy flux and mitochondrial biogenesis in the oxidative soleus muscle. We also observed increased basal autophagy flux and Bnip3 content without increases in autophagy protein expression in the plantaris muscle of sedentary muscle‐specific Pgc‐1α. transgenic mice, a genetic model of augmented mitochondrial biogenesis. These findings reveal that endurance exercise training‐induced increases in basal autophagy, including mitophagy, only take place if an enhanced oxidative phenotype is achieved. However, autophagy protein expression is mainly dictated by contractile activity independently of enhancements in oxidative phenotype. Exercise‐trained mice heterozygous for the critical autophagy protein Atg6 showed attenuated increases of basal autophagy flux, mitochondrial content, and angiogenesis in skeletal muscle, along with impaired improvement of endurance capacity. These results demonstrate that increased basal autophagy is required for endurance exercise training‐induced skeletal muscle adaptation and improvement of physical performance.—Lira, V. A., Okutsu, M., Zhang, M., Greene, N. P., Laker, R. C., Breen, D. S., Hoehn, K. L., Yan, Z., Autophagy is required for exercise training‐induced skeletal muscle adaptation and improvement of physical performance. FASEB J. 27, 4184–4193 (2013). www.fasebj.org
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In the citing paper
“Lira et al. report that an increase in basal autophagy is required for exercise training adaptations (39).”
From Chronological Age Does not Influence Ex-vivo Mitochondrial Respiration and Quality Control in Skeletal Muscle (2016) · cites this paper as [39]
In the citing paper
“The acute deletion of ATG7, specifically in skeletal muscle, does not affect exercise performance suggesting that autophagy is not required to sustain muscle contraction during exercise training [222, 223].”
From The connection between the dynamic remodeling of the mitochondrial network and the regulation of muscle mass (2021) · cites this paper as [223]
In the citing paper
“Importantly, both exercise methods can activate autophagic signaling in the aged skeletal muscle [15].”
From Lifelong Aerobic Exercise Alleviates Sarcopenia by Activating Autophagy and Inhibiting Protein Degradation via the AMPK/PGC-1α Signaling Pathway (2021) · cites this paper as [15]
In the citing paper
“it has been proposed that autophagy signals are necessary to achieve aerobic improvements in skeletal muscle (78).”
From Mitochondria initiate and regulate sarcopenia (2017) · cites this paper as [78]
In the citing paper
“Studies in rodents have shown an increased abundance of autophagy proteins including Drp1 and Bcl-2 and 19 kDa interacting protein-3 (Bnip3) after exercise (60, 65, 71, 78).”
From Mitochondria initiate and regulate sarcopenia (2017) · cites this paper as [78]
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Metadata
- Authors
- Lira, V. A., Okutsu, M., Zhang, M., Greene, N. P., Laker, R. C., Breen, D. S., Hoehn, K. L., & Yan, Z.
- Affiliations
- University of Virginia (US)
- Corresponding author
- Yan, Zhen
- ORCID
- Venue
- The FASEB Journal
- Publisher
- Wiley
- Published
- 2013-06-27
- Volume
- 27
- Issue
- 10
- Pages
- 4184-4193
- ISSN
- 0892-6638 (ISSN-L)
- 1530-6860
- PMC
- PMC4046188
- OpenAlex
- W2147459821
- Cited by
- 432
- References
- 45
- Citations by year
- 2026: 18 · 2025: 15 · 2024: 30 · 2023: 24 · 2022: 36 · 2021: 52 · 2020: 35 · 2019: 41 · 2018: 49 · 2017: 42 · 2016: 26 · 2015: 43 · 2014: 16 · 2013: 5
- FWCI
- 21.86
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The FASEB Journal (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (AR050429)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Medicine › Physiology (medical) › Exercise and Physiological Responses
- Keywords
- autophagy, exercise training, skeletal muscle adaptation, endurance exercise, mitophagy, BNIP3, mitochondrial biogenesis, oxidative muscle fibers, PGC-1α, LC3, p62, voluntary running, angiogenesis, endurance capacity, plantaris muscle, soleus muscle
- MeSH terms
- Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Adaptation, Physiological, Animals, Autophagy, Gene Expression Regulation, Male, Mice, Inbred C57BL, Mice, Transgenic, Physical Conditioning, Animal, Transcription Factors, Muscle, Skeletal, Mice
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