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Cited by 432Autophagy in Disease and TherapyMuscle Physiology and DisordersExercise and Physiological Responses

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

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Lira, Vitor A., Okutsu, Mitsuharu, Zhang, Mei, Greene, Nicholas P., Laker, Rhianna C., Breen, David S., Hoehn, Kyle L., Yan, Zhen·2013·The FASEB Journal
DOI 10.1096/fj.13-228486PMC PMC4046188
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Abstract

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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Crossref · 10.1096/fj.13-228486

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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
DOI
10.1096/fj.13-228486
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
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
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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