Journal article
Autophagy is required for exercise training-induced skeletal muscle adaptation and improvement of physical performance
The FASEB journal, Vol.27(10), pp.4184-4193
10/01/2013
DOI: 10.1096/fj.13-228486
PMCID: PMC4046188
PMID: 23825228
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-1 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.
Details
- Title: Subtitle
- Autophagy is required for exercise training-induced skeletal muscle adaptation and improvement of physical performance
- Creators
- Vitor A. Lira - University of VirginiaMitsuharu Okutsu - University of VirginiaMei Zhang - University of VirginiaNicholas P. Greene - University of VirginiaRhianna C. Laker - University of VirginiaDavid S. Breen - University of VirginiaKyle L. Hoehn - University of VirginiaZhen Yan - University of Virginia
- Resource Type
- Journal article
- Publication Details
- The FASEB journal, Vol.27(10), pp.4184-4193
- DOI
- 10.1096/fj.13-228486
- PMID
- 23825228
- PMCID
- PMC4046188
- NLM abbreviation
- FASEB J
- ISSN
- 0892-6638
- eISSN
- 1530-6860
- Publisher
- Wiley
- Number of pages
- 10
- Grant note
- T32HL07284 / NIH training grant; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA R01AR050429 / NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Arthritis & Musculoskeletal & Skin Diseases (NIAMS) AR050429 / U.S. National Institutes of Health (NIH); United States Department of Health & Human Services; National Institutes of Health (NIH) - USA American Physiological Society postdoctoral fellowship in physiological genomics 7-06-RA-165 / American Diabetes Association research award; American Diabetes Association T32HL007284 / NATIONAL HEART, LUNG, AND BLOOD INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI)
- Language
- English
- Date published
- 10/01/2013
- Academic Unit
- Health, Sport, and Human Physiology
- Record Identifier
- 9984259638102771
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