Autophagy is not required to sustain exercise and PRKAA1/AMPK activity but is important to prevent mitochondrial damage during physical activity
Open accessAbstract
Physical activity has been recently documented to play a fundamental physiological role in the regulation of autophagy in several tissues. It has also been reported that autophagy is required for exercise itself and for training-induced adaptations in glucose homeostasis. These autophagy-mediated metabolic improvements are thought to be largely dependent on the activation of the metabolic sensor PRKAA1/AMPK. However, it is unknown whether these important benefits stem from systemic adaptations or are due solely to alterations in skeletal muscle metabolism. To address this we utilized inducible, muscle-specific, atg7 knockout mice that we have recently generated. Our findings indicate that acute inhibition of autophagy in skeletal muscle just prior to exercise does not have an impact on physical performance, PRKAA1 activation, or glucose homeostasis. However, we reveal that autophagy is critical for the preservation of mitochondrial function during damaging muscle contraction. This effect appears to be gender specific affecting primarily females. We also establish that basal oxidative stress plays a crucial role in mitochondrial maintenance during normal physical activity. Therefore, autophagy is an adaptive response to exercise that ensures effective mitochondrial quality control during damaging physical activity.
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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.
“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 [222]
Mitophagy activation removes dysfunctional mitochondria that have been altered by exercise-dependent ROS production.
“Moreover, mitophagy activation removes dysfunctional mitochondria that have been altered by exercise-dependent ROS production [222].”
From The connection between the dynamic remodeling of the mitochondrial network and the regulation of muscle mass (2021) · cites this paper as [222]
Activation of autophagy during exercise is important for maintaining muscle energy homeostasis.
“However, the activation of autophagy during exercise is important for maintaining muscle energy homeostasis.”
From The connection between the dynamic remodeling of the mitochondrial network and the regulation of muscle mass (2021) · cites this paper as [222]
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1 retracted
Safdar, A., Bourgeois, J. M., Ogborn, D. I., Little, J. P., Hettinga, B. P., Akhtar, M., Thompson, J. E., Melov, S., Mocellin, N. J., Kujoth, G. C., et al. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1019581108 · Cited by 358 · see citing works
RetractedRepertoires of Autophagy in the Pathogenesis of Ocular Diseases
Li, Y., Jiang, Q. L., Cao, G.-F., Yao, J., & Yan, B. (2015) · Cellular Physiology and Biochemistry · doi:10.1159/000373980 · Cited by 16,351 · see citing works
Autophagy in the Pathogenesis of Disease
Levine, B., & Kroemer, G. (2008) · Cell · doi:10.1016/j.cell.2007.12.018 · Cited by 7,069 · see citing works
Autophagy: Renovation of Cells and Tissues
Mizushima, N., & Komatsu, M. (2011) · Cell · doi:10.1016/j.cell.2011.10.026 · Cited by 6,467 · see citing works
Autophagy and Viruses: Adversaries or Allies?
Dong, X., & Levine, B. (2013) · Journal of Innate Immunity · doi:10.1159/000346388 · Cited by 4,441 · see citing works
Succinate is an inflammatory signal that induces IL-1β through HIF-1α
Tannahill, G. M., Curtis, A. M., Adamik, J., Palsson-McDermott, E. M., McGettrick, A. F., Goel, G., Frezza, C., Bernard, N. J., Kelly, B., Foley, N. H., et al. (2013) · Nature · doi:10.1038/nature11986 · Cited by 4,176 · see citing works
Sandri, M., Sandri, C., Gilbert, A., Skurk, C., Calabria, E., Picard, A., Walsh, K., Schiaffino, S., Lecker, S. H., & Goldberg, A. L. (2004) · Cell · doi:10.1016/s0092-8674(04)00400-3 · Cited by 3,012 · see citing works
Self-citationMizushima, N., Yamamoto, A., Matsui, M., Yoshimori, T., & Ohsumi, Y. (2003) · Molecular Biology of the Cell · doi:10.1091/mbc.e03-09-0704 · Cited by 2,323 · see citing works
Rubinsztein, D. C., Mariño, G., & Kroemer, G. (2011) · Cell · doi:10.1016/j.cell.2011.07.030 · Cited by 2,107 · see citing works
Zoncu, R., Bar-Peled, L., Efeyan, A., Wang, S., Sancak, Y., & Sabatini, D. M. (2011) · Science · doi:10.1126/science.1207056 · Cited by 1,673 · see citing works
Antioxidants prevent health-promoting effects of physical exercise in humans
Ristow, M., Zarse, K., Oberbach, A., Klöting, N., Birringer, M., Kiehntopf, M., Stumvoll, M., Kahn, C. R., & Blüher, M. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0903485106 · Cited by 1,582 · see citing works
Mechanisms regulating skeletal muscle growth and atrophy
Schiaffino, S., Dyar, K. A., Ciciliot, S., Blaauw, B., & Sandri, M. (2013) · The FEBS Journal · doi:10.1111/febs.12253 · Cited by 1,492 · see citing works
Self-citationAutophagy is required to maintain muscle mass.
Masiero, E., Agatea, L., Mammucari, C., Blaauw, B., Loro, E., Komatsu, M., Metzger, D., Reggiani, C., Schiaffino, S., & Sandri, M. (2009) · Cell Metabolism · doi:10.1016/j.cmet.2009.10.008 · Cited by 1,282 · see citing works
Self-citationExercise-induced BCL2-regulated autophagy is required for muscle glucose homeostasis
He, C., Bassik, M. C., Moresi, V., Sun, K., Wei, Y., Zou, Z., An, Z., Loh, J., Fisher, J., Sun, Q., et al. (2012) · Nature · doi:10.1038/nature10758 · Cited by 1,136 · see citing works
Hanson, G. T., Aggeler, R., Oglesbee, D., Cannon, M., Capaldi, R. A., Tsien, R. Y., & Remington, S. J. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m312846200 · Cited by 988 · see citing works
Imaging Dynamic Redox Changes in Mammalian Cells with Green Fluorescent Protein Indicators
Dooley, C. T., Dore, T. M., Hanson, G. T., Jackson, W. C., Remington, S. J., & Tsien, R. Y. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m312847200 · Cited by 776 · see citing works
Kim, K. H., Jeong, Y. T., Oh, H., Kim, S. H., Cho, J. M., Kim, Y.-N., Kim, S. S., Kim, D. H., Hur, K. Y., Kim, H. K., et al. (2013) · Nature Medicine · doi:10.1038/nm.3014 · Cited by 774 · see citing works
Therapeutic Targeting of Mitochondrial Superoxide in Hypertension
Dikalova, A., Bikineyeva, A. T., Budzyn, K., Nazarewicz, R. R., McCann, L. A., Lewis, W., Harrison, D. G., & Dikalov, S. (2010) · Circulation Research · doi:10.1161/circresaha.109.214601 · Cited by 737 · see citing works
Mitochondrial fission and remodelling contributes to muscle atrophy
Romanello, V., Guadagnin, E., Gomes, L., Roder, I., Sandri, C., Petersen, Y., Milan, G., Masiero, E., Del Piccolo, P., Foretz, M., et al. (2010) · The EMBO Journal · doi:10.1038/emboj.2010.60 · Cited by 596 · see citing works
Self-citationRegulation of lipid stores and metabolism by lipophagy
Liu, K., & Czaja, M. J. (2013) · Cell Death & Differentiation · doi:10.1038/cdd.2012.63 · Cited by 542 · see citing works
Grumati, P., Coletto, L., Sabatelli, P., Cescon, M., Angelin, A., Bertaggia, E., Blaauw, B., Urciuolo, A., Tiepolo, T., Merlini, L., et al. (2010) · Nature Medicine · doi:10.1038/nm.2247 · Cited by 540 · see citing works
Self-citationHaem oxygenase is synthetically lethal with the tumour suppressor fumarate hydratase
Frezza, C., Zheng, L., Folger, O., Rajagopalan, K. N., MacKenzie, E. D., Jerby, L., Micaroni, M., Chaneton, B., Adam, J., Hedley, A., et al. (2011) · Nature · doi:10.1038/nature10363 · Cited by 503 · see citing works
Lira, V. A., Okutsu, M., Zhang, M., Greene, N. P., Laker, R. C., Breen, D. S., Hoehn, K. L., & Yan, Z. (2013) · The FASEB Journal · doi:10.1096/fj.13-228486 · Cited by 432 · see citing works
Resistance Exercise Reverses Aging in Human Skeletal Muscle
Melov, S., Tarnopolsky, M. A., Beckman, K. B., Felkey, K., & Hubbard, A. (2007) · PLoS ONE · doi:10.1371/journal.pone.0000465 · Cited by 344 · see citing works
Sandri, M., Barberi, L., Bijlsma, A. Y., Blaauw, B., Dyar, K. A., Milan, G., Mammucari, C., Meskers, C. G. M., Pallafacchina, G., Paoli, A., et al. (2013) · Biogerontology · doi:10.1007/s10522-013-9432-9 · Cited by 340 · see citing works
Self-citationCoen, P. M., Jubrias, S. A., Distefano, G., Amati, F., Mackey, D. C., Glynn, N. W., Manini, T. M., Wohlgemuth, S. E., Leeuwenburgh, C., Cummings, S. R., et al. (2013) · The Journals of Gerontology: Series A · doi:10.1093/gerona/gls196 · Cited by 323 · see citing works
Autophagy as a new therapeutic target in Duchenne muscular dystrophy
De Palma, C., Morisi, F., Cheli, S., Pambianco, S., Cappello, V, Vezzoli, M., Rovere-Querini, P., Moggio, M., Ripolone, M., Francolini, M., et al. (2012) · Cell Death & Disease · doi:10.1038/cddis.2012.159 · Cited by 269 · see citing works
Self-citationThe Mitochondrial Chaperone TRAP1 Promotes Neoplastic Growth by Inhibiting Succinate Dehydrogenase
Sciacovelli, M., Guzzo, G., Morello, V., Frezza, C., Zheng, L., Nannini, N., Calabrese, F., Laudiero, G., Esposito, F., Landriscina, M., et al. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.04.019 · Cited by 269 · see citing works
Grumati, P., Coletto, L., Schiavinato, A., Castagnaro, S., Bertaggia, E., Sandri, M., & Bonaldo, P. (2011) · Autophagy · doi:10.4161/auto.7.12.17877 · Cited by 267 · see citing works
Self-citationExercise induces autophagy in peripheral tissues and in the brain
He, C., Sumpter, R., & Levine, B. (2012) · Autophagy · doi:10.4161/auto.21327 · Cited by 259 · see citing works
Modulation of glutamine metabolism by the PI(3)K–PKB–FOXO network regulates autophagy
van der Vos, K. E., Eliasson, P., Proikas‐Cezanne, T., Vervoort, S. J., van Boxtel, R., Putker, M., van Zutphen, I. J., Mauthe, M., Zellmer, S., Pals, C. E. G. M., et al. (2012) · Nature Cell Biology · doi:10.1038/ncb2536 · Cited by 246 · see citing works
Autophagy inhibition induces atrophy and myopathy in adult skeletal muscles
Masiero, E., & Sandri, M. (2010) · Autophagy · doi:10.4161/auto.6.2.11137 · Cited by 220 · see citing works
Self-citationFontana, L., Klein, S., & Holloszy, J. O. (2009) · AGE · doi:10.1007/s11357-009-9118-z · Cited by 178 · see citing works
The role of autophagy in the pathogenesis of glycogen storage disease type II (GSDII)
Nascimbeni, A. C., Fanin, M., Masiero, E., Angelini, C. I., & Sandri, M. (2012) · Cell Death and Differentiation · doi:10.1038/cdd.2012.52 · Cited by 106 · see citing works
Self-citationToledo, F. G. S., & Goodpaster, B. H. (2013) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2013.06.018 · Cited by 82 · see citing works
Impaired autophagy contributes to muscle atrophy in glycogen storage disease type II patients
Nascimbeni, A. C., Fanin, M., Masiero, E., Angelini, C. I., & Sandri, M. (2012) · Autophagy · doi:10.4161/auto.21691 · Cited by 68 · see citing works
Self-citationFOXOphagy path to inducing stress resistance and cell survival
Sandri, M. (2012) · Nature Cell Biology · doi:10.1038/ncb2550 · Cited by 53 · see citing works
Self-citationEffects of endurance training on apoptotic susceptibility in striated muscle
Vainshtein, A., Kazak, L., & Hood, D. A. (2011) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00020.2011 · Cited by 37 · see citing works
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- Authors
- Lo Verso, F., Carnio, S., Vainshtein, A., & Sandri, M.
- Affiliations
- Veneto Institute of Molecular Medicine (IT)
- York University (CA)
- University of Padua (IT)
- Corresponding author
- Sandri, Marco
- Venue
- Autophagy
- Publisher
- Informa UK Limited
- Published
- 2014-10-30
- Volume
- 10
- Issue
- 11
- Pages
- 1883-1894
- ISSN
- 1554-8627 (ISSN-L)
- 1554-8635
- PMC
- PMC4502666
- OpenAlex
- W1994408958
- Cited by
- 146
- References
- 38
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 12 · 2023: 13 · 2022: 6 · 2021: 21 · 2020: 11 · 2019: 12 · 2018: 20 · 2017: 13 · 2016: 16 · 2015: 12
- FWCI
- 10.32
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Autophagy (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Figshare (submittedVersion, cc-by)
- Padua Research Archive (University of Padova) (submittedVersion)
- Figshare (cc-by)
- Funders
- Fondation Leducq
- Fondazione Telethon
- Consiglio Nazionale delle Ricerche
- Topics
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Health Sciences › Medicine › Rehabilitation › Exercise and Physiological Responses
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- physical activity, skeletal muscle, mitochondrial damage, mitochondrial quality control, oxidative stress, muscle contraction, glucose homeostasis, sex differences, physical performance
- MeSH terms
- Autophagy-Related Protein 7, Animals, Antioxidants, Autophagy, Female, Glucose, Homeostasis, Male, Microtubule-Associated Proteins, Mitochondria, Muscle Contraction, Physical Conditioning, Animal, Mice, Knockout, Oxidative Stress, Mice, AMP-Activated Protein Kinases
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