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
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
An increase in basal autophagy is required for exercise training adaptations.
“Lira et al. report that an increase in basal autophagy is required for exercise training adaptations (39).”
From Chronological Age Does not Influence<i>Ex-vivo</i>Mitochondrial Respiration and Quality Control in Skeletal Muscle (2016) · cites this paper as [39]
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 [223]
Both resistance and aerobic exercise can activate autophagic signaling in aged skeletal muscle.
“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]
Autophagy signals are necessary to achieve aerobic improvements in skeletal muscle.
“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]
Studies in rodents show increased abundance of autophagy proteins including Drp1, Bcl-2, and Bnip3 after exercise.
“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]
Cites
1 retracted
Wenz, T., Rossi, S. G., Rotundo, R. L., Spiegelman, B. M., & Moraes, C. T. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0911570106 · Cited by 600 · see citing works
RetractedLC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing.
Kabeya, Y., Mizushima, N., Ueno, T., Yamamoto, A., Kirisako, T., Noda, T., Kominami, E., Ohsumi, Y., & Yoshimori, T. (2000) · The EMBO Journal · doi:10.1093/emboj/19.21.5720 · Cited by 6,605 · see citing works
Autophagy fights disease through cellular self-digestion
Mizushima, N., Levine, B., Cuervo, A. M., & Klionsky, D. J. (2008) · Nature · doi:10.1038/nature06639 · Cited by 6,452 · see citing works
Levine, B., & Klionsky, D. J. (2004) · Developmental Cell · doi:10.1016/s1534-5807(04)00099-1 · Cited by 3,671 · see citing works
Kodama, S. (2009) · JAMA · doi:10.1001/jama.2009.681 · Cited by 3,035 · see citing works
Fiber Types in Mammalian Skeletal Muscles
Schiaffino, S., & Reggiani, C. (2011) · Physiological Reviews · doi:10.1152/physrev.00031.2010 · Cited by 3,022 · see citing works
Diet, lifestyle, and the risk of type 2 diabetes mellitus in women.
Hu, F. B., Manson, J. E., Stampfer, M. J., Colditz, G., Liu, S., Solomon, C. G., & Willett, W. C. (2001) · New England Journal of Medicine · doi:10.1056/nejmoa010492 · Cited by 2,901 · see citing works
Transcriptional co-activator PGC-1α drives the formation of slow-twitch muscle fibres
Lin, J., Wu, H., Tarr, P. T., Zhang, C.-Y., Wu, Z., Boss, O., Michael, L. F., Puigserver, P., Isotani, E., Olson, E. N., et al. (2002) · Nature · doi:10.1038/nature00904 · Cited by 2,546 · see citing works
Promotion of tumorigenesis by heterozygous disruption of the beclin 1 autophagy gene
Qu, X., Yu, J., Bhagat, G., Furuya, N., Hibshoosh, H., Troxel, A., Rosen, J., Eskelinen, E.-L., Mizushima, N., Ohsumi, Y., et al. (2003) · Journal of Clinical Investigation · doi:10.1172/jci20039 · Cited by 2,311 · see citing works
DeFronzo, R. A., Jacot, E., Jequier, E., Maeder, E., Wahren, J., & Felber, J. P. (1981) · Diabetes · doi:10.2337/diab.30.12.1000 · Cited by 1,770 · see citing works
Regulation of Mammalian Autophagy in Physiology and Pathophysiology
Ravikumar, B., Sarkar, S., Davies, J. E., Futter, M., Garcı́a-Arencibia, M., Green-Thompson, Z. W., Jiménez-Sánchez, M., Korolchuk, V. I., Lichtenberg, M., Luo, S., et al. (2010) · Physiological Reviews · doi:10.1152/physrev.00030.2009 · Cited by 1,726 · see citing works
Estimation of skeletal muscle mass by bioelectrical impedance analysis
Janssen, I., Heymsfield, S. B., Baumgartner, R. N., & Ross, R. (2000) · Journal of Applied Physiology · doi:10.1152/jappl.2000.89.2.465 · Cited by 1,482 · see citing works
Lemasters, J. J. (2005) · Rejuvenation Research · doi:10.1089/rej.2005.8.3 · Cited by 1,342 · see citing works
Autophagy 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
Exercise-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
Role of BNIP3 and NIX in cell death, autophagy, and mitophagy
Zhang, J., & Ney, P. A. (2009) · Cell Death & Differentiation · doi:10.1038/cdd.2009.16 · Cited by 1,021 · see citing works
Manson, J. E., Hu, F. B., Rich-Edwards, J. W., Colditz, G. A., Stampfer, M. J., Willett, W. C., Speizer, F. E., & Hennekens, C. H. (1999) · New England Journal of Medicine · doi:10.1056/nejm199908263410904 · Cited by 1,005 · see citing works
Individual differences in response to regular physical activity
BOUCHARD, C., & RANKINEN, T. (2001) · Medicine and Science in Sports and Exercise · doi:10.1097/00005768-200106001-00013 · Cited by 939 · see citing works
HDAC6 controls autophagosome maturation essential for ubiquitin‐selective quality‐control autophagy
Lee, J., Koga, H., Kawaguchi, Y., Tang, W., Wong, E., Gao, Y., Pandey, U. B., Kaushik, S., Tresse, E., Lu, J., et al. (2010) · The EMBO Journal · doi:10.1038/emboj.2009.405 · Cited by 756 · see citing works
Total daily physical activity and the risk of AD and cognitive decline in older adults
Buchman, A. S., Boyle, P. A., Yu, L., Shah, R. C., Wilson, R. S., & Bennett, D. A. (2012) · Neurology · doi:10.1212/wnl.0b013e3182535d35 · Cited by 730 · 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
The Role of Autophagy in Mammalian Development: Cell Makeover Rather than Cell Death
Cecconi, F., & Levine, B. (2008) · Developmental Cell · doi:10.1016/j.devcel.2008.08.012 · Cited by 521 · see citing works
Synergistic interaction between exercise and insulin on peripheral glucose uptake.
DeFronzo, R. A., Ferrannini, E., Sato, Y., Felig, P., & Wahren, J. (1981) · Journal of Clinical Investigation · doi:10.1172/jci110399 · Cited by 415 · see citing works
PGC-1α regulation by exercise training and its influences on muscle function and insulin sensitivity
Lira, V. A., Benton, C. R., Yan, Z., & Bonen, A. (2010) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00755.2009 · Cited by 412 · see citing works
Self-citationWohlgemuth, S. E., Seo, A. Y., Marzetti, E., Lees, H. A., & Leeuwenburgh, C. (2010) · Experimental Gerontology · doi:10.1016/j.exger.2009.11.002 · Cited by 397 · see citing works
Raben, N., Hill, V., Shea, L., Takikita, S., Baum, R., Mizushima, N., Ralston, E., & Plotz, P. (2008) · Human Molecular Genetics · doi:10.1093/hmg/ddn292 · Cited by 352 · see citing works
Yan, Z., Okutsu, M., Akhtar, Y., & Lira, V. A. (2010) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00993.2010 · Cited by 338 · see citing works
Self-citationPhysical activity and reduced risk of colon cancer: implications for prevention
Colditz, G. A., Cannuscio, C. C., & Frazier, A. L. (1997) · Cancer Causes & Control · doi:10.1023/a:1018458700185 · Cited by 311 · see citing works
Splanchnic and Peripheral Disposal of Oral Glucose in Man
Katz, L. D., Glickman, M. G., Rapoport, S. I., Ferrannini, E., & DeFronzo, R. A. (1983) · Diabetes · doi:10.2337/diab.32.7.675 · Cited by 287 · 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
Geng, T., Li, P., Okutsu, M., Yin, X., Kwek, J., Zhang, M., & Yan, Z. (2010) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00481.2009 · Cited by 263 · see citing works
Self-citationQuinsay, M. N., Thomas, R. L., Lee, Y., & Gustafsson, Å. B. (2010) · Autophagy · doi:10.4161/auto.6.7.13005 · Cited by 239 · see citing works
Autophagy in health and disease. 5. Mitophagy as a way of life
Gottlieb, R. A., & Carreira, R. (2010) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00097.2010 · Cited by 228 · 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
Voluntary running induces fiber type-specific angiogenesis in mouse skeletal muscle
Waters, R. E., Rotevatn, S., Li, P., Annex, B. H., & Yan, Z. (2004) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00247.2004 · Cited by 214 · see citing works
Self-citationAutophagy in Health and Disease
Gözüaçık, D. (2013) · Elsevier eBooks · doi:10.1016/c2010-0-66523-0 · Cited by 194 · see citing works
Nitric oxide and AMPK cooperatively regulate PGC-1α in skeletal muscle cells
Lira, V. A., Brown, D. L., Lira, A. K., Kavazis, A. N., Soltow, Q. A., Zeanah, E. H., & Criswell, D. S. (2010) · The Journal of Physiology · doi:10.1113/jphysiol.2010.194035 · Cited by 185 · see citing works
Self-citationPogozelski, A. R., Geng, T., Li, P., Yin, X., Lira, V. A., Zhang, M., Chi, J.-T., & Yan, Z. (2009) · PLoS ONE · doi:10.1371/journal.pone.0007934 · Cited by 164 · see citing works
Self-citationExercise protects against doxorubicin-induced markers of autophagy signaling in skeletal muscle
Smuder, A. J., Kavazis, A. N., Min, K., & Powers, S. K. (2011) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00429.2011 · Cited by 131 · see citing works
Akimoto, T., Ribar, T. J., Williams, R. S., & Yan, Z. (2004) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00248.2004 · Cited by 124 · see citing works
Self-citationYamada, E., Bastie, C. C., Koga, H., Wang, Y., Cuervo, A. M., & Pessin, J. E. (2012) · Cell Reports · doi:10.1016/j.celrep.2012.03.014 · Cited by 103 · see citing works
Band, M., Joel, A., Hernandez, A. G., & Avivi, A. (2009) · The FASEB Journal · doi:10.1096/fj.08-122978 · Cited by 93 · see citing works
Li, P., Akimoto, T., Zhang, M., Williams, R. S., & Yan, Z. (2006) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00532.2005 · Cited by 63 · see citing works
Self-citationNielsen, J., Suetta, C., Hvid, L. G., Schrøder, H. D., Aagaard, P., & Ørtenblad, N. (2010) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00324.2010 · Cited by 61 · see citing works
Blood flow, mitochondria, and performance in skeletal muscle after denervation and reinnervation
Eisenberg, H. A., & Hood, D. A. (1994) · Journal of Applied Physiology · doi:10.1152/jappl.1994.76.2.859 · Cited by 48 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Mitochondrial dynamics in health and disease: mechanisms and potential targets
Chen, W., Zhao, H., & Li, Y. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01547-9 · Cited by 1,306 · see citing works
Autophagy—a key player in cellular and body metabolism
Kim, K. H., & Lee, M. (2014) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2014.35 · Cited by 962 · see citing works
Maintenance of Skeletal Muscle Mitochondria in Health, Exercise, and Aging
Hood, D. A., Memme, J. M., Oliveira, A. N., & Triolo, M. (2019) · Annual Review of Physiology · doi:10.1146/annurev-physiol-020518-114310 · Cited by 567 · see citing works
Laker, R. C., Drake, J. C., Wilson, R. J., Lira, V. A., Lewellen, B. M., Ryall, K. A., Fisher, C. C., Zhang, M., Saucerman, J. J., Goodyear, L. J., et al. (2017) · Nature Communications · doi:10.1038/s41467-017-00520-9 · Cited by 529 · see citing works
Self-citationMitochondrial quality control and muscle mass maintenance.
Romanello, V., & Sandri, M. (2016) · Frontiers in Physiology · doi:10.3389/fphys.2015.00422 · Cited by 434 · see citing works
Autophagy and the cell biology of age-related disease
Leidal, A. M., Levine, B., & Debnath, J. (2018) · Nature Cell Biology · doi:10.1038/s41556-018-0235-8 · Cited by 424 · see citing works
PGC-1α-mediated regulation of mitochondrial function and physiological implications
Halling, J. F., & Pilegaard, H. (2020) · Applied Physiology, Nutrition, and Metabolism · doi:10.1139/apnm-2020-0005 · Cited by 418 · see citing works
Autophagy in metabolic disease and ageing
Kitada, M., & Koya, D. (2021) · Nature Reviews Endocrinology · doi:10.1038/s41574-021-00551-9 · Cited by 413 · see citing works
Autophagy in liver diseases: A review
Qian, H., Chao, X., Williams, J. A. R., Fulte, S., Li, T., Yang, L., & Ding, W. (2021) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2021.100973 · Cited by 377 · see citing works
Physical Activity and Brain Health
Liegro, C. M. D., Schiera, G., Proia, P., & Liegro, I. D. (2019) · Genes · doi:10.3390/genes10090720 · Cited by 392 · see citing works
Exercise and mitochondrial health
Memme, J. M., Erlich, A. T., Phukan, G., & Hood, D. A. (2021) · The Journal of Physiology · doi:10.1113/jp278853 · Cited by 343 · see citing works
Muscle fiber type diversification during exercise and regeneration
Qaisar, R., Bhaskaran, S., & Van Remmen, H. (2016) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2016.03.025 · Cited by 283 · see citing works
Molecular mechanisms for mitochondrial adaptation to exercise training in skeletal muscle
Drake, J. C., Wilson, R. J., & Yan, Z. (2016) · The FASEB Journal · doi:10.1096/fj.15-276337 · Cited by 263 · see citing works
Self-citationRole of PGC-1α during acute exercise-induced autophagy and mitophagy in skeletal muscle
Vainshtein, A., Tryon, L. D., Pauly, M., & Hood, D. A. (2015) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00380.2014 · Cited by 273 · see citing works
Egan, B., & Sharples, A. P. (2023) · Physiological Reviews · doi:10.1152/physrev.00054.2021 · Cited by 278 · see citing works
Exercise sustains the hallmarks of health
Qiu, Y., Fernández-García, B., Lehmann, H. I., Li, G., Kroemer, G., López-Otín, C., & Xiao, J. (2023) · Journal of Sport and Health Science · doi:10.1016/j.jshs.2022.10.003 · Cited by 270 · see citing works
Heat shock response and autophagy—cooperation and control
Dokładny, K., Myers, O., & Moseley, P. L. (2015) · Autophagy · doi:10.1080/15548627.2015.1009776 · Cited by 254 · see citing works
Mitophagy pathways in health and disease
Killackey, S. A., Philpott, D. J., & Girardin, S. E. (2020) · The Journal of Cell Biology · doi:10.1083/jcb.202004029 · Cited by 236 · see citing works
Laker, R., Lillard, T. S., Okutsu, M., Zhang, M., Hoehn, K. L., Connelly, J., & Yan, Z. (2014) · Diabetes · doi:10.2337/db13-1614 · Cited by 205 · see citing works
Self-citationEvolving and Expanding the Roles of Mitophagy as a Homeostatic and Pathogenic Process
Gustafsson, Å. B., & Dorn, G. W. (2018) · Physiological Reviews · doi:10.1152/physrev.00005.2018 · Cited by 229 · see citing works
Autophagy and aging: Maintaining the proteome through exercise and caloric restriction
Escobar, K. A., Cole, N. H., Mermier, C. M., & VanDusseldorp, T. A. (2018) · Aging Cell · doi:10.1111/acel.12876 · Cited by 226 · see citing works
Liu, Y., Palanivel, R., Rai, E., Park, M. S., Gabor, T. V., Scheid, M. P., Xu, A., & Sweeney, G. (2014) · Diabetes · doi:10.2337/db14-0267 · Cited by 223 · see citing works
Signaling Pathways That Control Muscle Mass
Vainshtein, A., & Sandri, M. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21134759 · Cited by 213 · see citing works
Romanello, V., & Sandri, M. (2021) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-020-03662-0 · Cited by 197 · see citing works
Qiao, S., Dennis, M. J., Song, X., Vadysirisack, D. D., Salunke, D., Nash, Z. M., Yang, Z., Liesa, M., Yoshioka, J., Matsuzawa, S., et al. (2015) · Nature Communications · doi:10.1038/ncomms8014 · Cited by 196 · see citing works
Mitochondria, Muscle Health, and Exercise with Advancing Age
Carter, H. N., Chen, C. C. W., & Hood, D. A. (2015) · Physiology · doi:10.1152/physiol.00039.2014 · Cited by 191 · see citing works
Joseph, A., Adhihetty, P. J., & Leeuwenburgh, C. (2016) · The Journal of Physiology · doi:10.1113/jp270659 · Cited by 186 · see citing works
VanderVeen, B. N., Fix, D. K., & Carson, J. A. (2017) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2017/3292087 · Cited by 182 · see citing works
Sarcoplasmic reticulum–mitochondria communication in cardiovascular pathophysiology
López‐Crisosto, C., Pennanen, C., Vásquez-Trincado, C., Morales, P. E., Bravo, R., Quest, A. F. G., Chiong, M., & Lavandero, S. (2017) · Nature Reviews Cardiology · doi:10.1038/nrcardio.2017.23 · Cited by 183 · see citing works
Chen, L., Qin, Y. H., Liu, B., Gao, M. Q., Li, A., Li, X., & Gong, G. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.871357 · Cited by 172 · see citing works
Schwalm, C., Jamart, C., Benoit, N., Naslain, D., Prémont, C., Prévet, J., Thienen, R. V., Deldicque, L., & Francaux, M. (2015) · The FASEB Journal · doi:10.1096/fj.14-267187 · Cited by 174 · see citing works
Ulbricht, A., Gehlert, S., Leciejewski, B., Schiffer, T., Bloch, W., & Höhfeld, J. (2015) · Autophagy · doi:10.1080/15548627.2015.1017186 · Cited by 169 · see citing works
Mijwel, S., Cardinale, D. A., Norrbom, J., Chapman, M., Ivarsson, N., Wengström, Y., Sundberg, C. J., & Rundqvist, H. (2018) · The FASEB Journal · doi:10.1096/fj.201700968r · Cited by 167 · see citing works
Unravelling the mechanisms regulating muscle mitochondrial biogenesis
Hood, D. A., Tryon, L. D., Carter, H. N., Kim, Y., & Chen, C. C. W. (2016) · Biochemical Journal · doi:10.1042/bcj20160009 · Cited by 159 · see citing works
Electrical Stimulation Counteracts Muscle Decline in Seniors
Kern, H., Barberi, L., Löfler, S., Sbardella, S., Burggraf, S., Fruhmann, H., Carraro, U., Mosole, S., Šarabon, N., Vogelauer, M., et al. (2014) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2014.00189 · Cited by 163 · see citing works
Mitochondria initiate and regulate sarcopenia
Alway, S. E., Mohamed, J. S., & Myers, M. J. (2017) · Exercise and Sport Sciences Reviews · doi:10.1249/jes.0000000000000101 · Cited by 153 · see citing works
“Indeed, it has been proposed that autophagy signals are necessary to achieve aerobic improvements in skeletal muscle (78).”
BackgroundImpacts of exercise interventions on different diseases and organ functions in mice
Guo, S., Huang, Y., Yan, Z., Huang, H., Hong, S., & Liu, T. (2019) · Journal of sport and health science/Journal of Sport and Health Science · doi:10.1016/j.jshs.2019.07.004 · Cited by 150 · see citing works
Self-citationLo Verso, F., Carnio, S., Vainshtein, A., & Sandri, M. (2014) · Autophagy · doi:10.4161/auto.32154 · Cited by 146 · see citing works
Jamart, C., Naslain, D., Gilson, H., & Francaux, M. (2013) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00270.2013 · Cited by 148 · see citing works
Cachexia in chronic obstructive pulmonary disease: new insights and therapeutic perspective
Sanders, K. J. C., Kneppers, A. E. M., van de Bool, C., LANGEN, R. C. J., & Schols, A. M. W. J. (2015) · Journal of Cachexia Sarcopenia and Muscle · doi:10.1002/jcsm.12062 · Cited by 149 · see citing works
Exercise Induces Tissue-Specific Adaptations to Enhance Cardiometabolic Health
Ashcroft, S. P., Stocks, B., Egan, B., & Zierath, J. R. (2024) · Cell Metabolism · doi:10.1016/j.cmet.2023.12.008 · Cited by 149 · see citing works
Autophagy is essential to support skeletal muscle plasticity in response to endurance exercise
Sanchez, A. M. J., Bernardi, H., Py, G., & Candau, R. B. (2014) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00187.2014 · Cited by 143 · see citing works
Carter, H. N., Kim, Y., Erlich, A. T., Zarrin‐khat, D., & Hood, D. A. (2018) · The Journal of Physiology · doi:10.1113/jp275998 · Cited by 136 · see citing works
The physiopathologic role of oxidative stress in skeletal muscle
Scicchitano, B. M., Pelosi, L., Sica, G., & Musarò, A. (2017) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2017.08.009 · Cited by 141 · see citing works
Seals, D. R., Kaplon, R. E., Gioscia‐Ryan, R. A., & LaRocca, T. J. (2014) · Physiology · doi:10.1152/physiol.00059.2013 · Cited by 138 · see citing works
Vettor, R., Valerio, A., Ragni, M., Trevellin, E., Granzotto, M., Olivieri, M., Tedesco, L., Ruocco, C., Fossati, A., Fabris, R., et al. (2014) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00617.2013 · Cited by 132 · see citing works
The regulation of autophagy during exercise in skeletal muscle
Vainshtein, A., & Hood, D. A. (2015) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00550.2015 · Cited by 132 · see citing works
Exercise activates lysosomal function in the brain through AMPK‐SIRT1‐TFEB pathway
Huang, J., Wang, X., Zhu, Y., Li, Z., Zhu, Y., Wu, J., Qin, Z., Xiang, M., & Lin, F. (2019) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.13114 · Cited by 129 · see citing works
Exercise-induced skeletal muscle signaling pathways and human athletic performance
Camera, D. M., Smiles, W. J., & Hawley, J. A. (2016) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2016.02.007 · Cited by 128 · see citing works
Ju, J.-S., Jeon, S.-I., Park, J.-Y., Lee, J.-Y., Lee, S.-C., Cho, K.-J., & Jeong, J.-M. (2016) · The Journal of Physiological Sciences · doi:10.1007/s12576-016-0440-9 · Cited by 125 · see citing works
The many roles of PGC-1α in muscle — recent developments
Chan, M. C., & Arany, Z. P. (2014) · Metabolism · doi:10.1016/j.metabol.2014.01.006 · Cited by 125 · see citing works
Axelrod, C. L., Fealy, C. E., Mulya, A., & Kirwan, J. P. (2018) · Acta Physiologica · doi:10.1111/apha.13216 · Cited by 120 · see citing works
Role of Parkin and endurance training on mitochondrial turnover in skeletal muscle
Chen, C. C. W., Erlich, A. T., & Hood, D. A. (2018) · Skeletal Muscle · doi:10.1186/s13395-018-0157-y · Cited by 124 · see citing works
Endurance Exercise and the Regulation of Skeletal Muscle Metabolism
Booth, F. W., Ruegsegger, G. N., Toedebusch, R. G., & Yan, Z. (2015) · Progress in molecular biology and translational science · doi:10.1016/bs.pmbts.2015.07.016 · Cited by 125 · see citing works
Self-citationExercise and exercise training-induced increase in autophagy markers in human skeletal muscle
Brandt, N., Gunnarsson, T. P., Bangsbo, J., & Pilegaard, H. (2018) · Physiological Reports · doi:10.14814/phy2.13651 · Cited by 120 · see citing works
The beneficial role of proteolysis in skeletal muscle growth and stress adaptation
Bell, R. A. V., Al-Khalaf, M. H., & Megeney, L. A. (2016) · Skeletal Muscle · doi:10.1186/s13395-016-0086-6 · Cited by 117 · see citing works
White, Z. R., Terrill, J. R., White, R. B., McMahon, C., Sheard, P., Grounds, M. D., & Shavlakadze, T. (2016) · Skeletal Muscle · doi:10.1186/s13395-016-0117-3 · Cited by 119 · see citing works
Franklin, B. A., Eijsvogels, T. M. H., Pandey, A., Quindry, J. C., & Toth, P. P. (2022) · American Journal of Preventive Cardiology · doi:10.1016/j.ajpc.2022.100424 · Cited by 127 · see citing works
Physical exercise increases autophagic signaling through ULK1 in human skeletal muscle
Møller, A. B., Vendelbo, M. H., Christensen, B., Clasen, B. F., Bak, A. M., Jørgensen, J. O. L., Møller, N., & Jessen, N. (2015) · Journal of Applied Physiology · doi:10.1152/japplphysiol.01116.2014 · Cited by 109 · see citing works
Exercise induces TFEB expression and activity in skeletal muscle in a PGC-1α-dependent manner
Erlich, A. T., Brownlee, D., Beyfuss, K. A., & Hood, D. A. (2017) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00162.2017 · Cited by 110 · see citing works
Autophagy as a Potential Target for Sarcopenia: AUTOPHAGY REGULATION IN SARCOPENIA
Fan, J., Kou, X., Jia, S., Yang, X., Yang, Y., & Chen, N. (2016) · Journal of Cellular Physiology · doi:10.1002/jcp.25260 · Cited by 101 · see citing works
Carson, J. A., Hardee, J. P., & VanderVeen, B. N. (2015) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2015.11.005 · Cited by 104 · see citing works
Fritzen, A. M., Madsen, A. B., Kleinert, M., Treebak, J. T., Lundsgaard, A., Jensen, T. E., Richter, E. A., Wojtaszewski, J. F. P., Kiens, B., & Frøsig, C. (2015) · The Journal of Physiology · doi:10.1113/jp271405 · Cited by 100 · see citing works
Mitochondrial Impairment in Sarcopenia
Bellanti, F., Buglio, A. L., & Vendemiale, G. (2021) · Biology · doi:10.3390/biology10010031 · Cited by 99 · see citing works
Lesmana, R., Sinha, R. A., Singh, B. K., Zhou, J., Ohba, K., Wu, Y., Yau, W. W. Y., Bay, B., & Yen, P. M. (2015) · Endocrinology · doi:10.1210/en.2015-1632 · Cited by 97 · see citing works
Cold and Exercise: Therapeutic Tools to Activate Brown Adipose Tissue and Combat Obesity
da Silva, C. P. V., Hernández‐Saavedra, D., White, J. D., & Stanford, K. (2019) · Biology · doi:10.3390/biology8010009 · Cited by 95 · see citing works
Excess Accumulation of Lipid Impairs Insulin Sensitivity in Skeletal Muscle
Park, S. S., & Seo, Y. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21061949 · Cited by 101 · see citing works
Wang, F., Xu, C., Reece, E. A., Li, X., Wu, Y., Harman, C. R., Yu, J., Dong, D., Wang, C., Yang, P., et al. (2017) · Nature Communications · doi:10.1038/ncomms15182 · Cited by 96 · see citing works
Greene, N. P., Lee, D. E., Brown, J. L., Rosa, M. E., Brown, L. A., Perry, R. A., Henry, J. N., & Washington, T. A. (2015) · Physiological Reports · doi:10.14814/phy2.12470 · Cited by 89 · see citing works
Self-citationBloemberg, D., & Quadrilatero, J. (2019) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00261.2018 · Cited by 93 · see citing works
Mitochondria and Aging—The Role of Exercise as a Countermeasure
Nilsson, M. I., & Tarnopolsky, M. A. (2019) · Biology · doi:10.3390/biology8020040 · Cited by 92 · see citing works
Mitochondrial Properties in Skeletal Muscle Fiber
Dong, H., & Tsai, S. (2023) · Cells · doi:10.3390/cells12172183 · Cited by 95 · see citing works
Vainshtein, A., Grumati, P., Sandri, M., & Bonaldo, P. (2014) · Journal of Molecular Medicine · doi:10.1007/s00109-013-1096-z · Cited by 88 · see citing works
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. (2016) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00066.2016 · Cited by 80 · see citing works
Nutrition and other lifestyle influences on arterial aging
LaRocca, T. J., Martens, C. R., & Seals, D. R. (2017) · Ageing Research Reviews · doi:10.1016/j.arr.2016.09.002 · Cited by 83 · see citing works
Sujkowski, A. L., Bazzell, B. G., Carpenter, K., Arking, R., & Wessells, R. J. (2015) · Aging · doi:10.18632/aging.100789 · Cited by 84 · see citing works
Kuramoto, K., Liang, H., Hong, J., & He, C. (2023) · Cell Metabolism · doi:10.1016/j.cmet.2023.01.011 · Cited by 86 · see citing works
Young, C., Sinadinos, A., Lefebvre, A., Chan, P., Arkle, S., Vaudry, D., & Górecki, D. C. (2015) · Autophagy · doi:10.4161/15548627.2014.994402 · Cited by 84 · see citing works
Liang, J., Zhang, H., Zeng, Z., Wu, L., Zhang, Y., Guo, Y., Lv, J., Wang, C., Fan, J., & Chen, N. (2021) · Metabolites · doi:10.3390/metabo11050323 · Cited by 84 · see citing works
Role of AMPK in regulation of LC3 lipidation as a marker of autophagy in skeletal muscle
Fritzen, A. M., Frøsig, C., Jeppesen, J. F., Jensen, T. E., Lundsgaard, A., Serup, A. K., Schjerling, P., Proud, C. G., Richter, E. A., & Kiens, B. (2016) · Cellular Signalling · doi:10.1016/j.cellsig.2016.03.005 · Cited by 82 · see citing works
Methods for Measuring Autophagy in Mice
Moulis, M., & Vindis, C. (2017) · Cells · doi:10.3390/cells6020014 · Cited by 79 · see citing works
Exercise-Induced Mitophagy in Skeletal Muscle and Heart
Guan, Y., Drake, J. C., & Yan, Z. (2019) · Exercise and Sport Sciences Reviews · doi:10.1249/jes.0000000000000192 · Cited by 79 · see citing works
Self-citationDistefano, G., Standley, R. A., Dubé, J. J., Carnero, E. A., Ritov, V. B., Stefanovic-Racic, M., Toledo, F. G. S., Piva, S. R., Goodpaster, B. H., & Coen, P. M. (2016) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/glw102 · Cited by 76 · see citing works
Call, J. A., Wilson, R. J., Laker, R. C., Zhang, M., Kundu, M., & Yan, Z. (2017) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00348.2016 · Cited by 77 · see citing works
Self-citationExercise‐mediated modulation of autophagy in skeletal muscle
Martín-Rincón, M., Morales‐Álamo, D., & Calbet, J. A. L. (2017) · Scandinavian Journal of Medicine and Science in Sports · doi:10.1111/sms.12945 · Cited by 76 · see citing works
Mitophagy is required for brown adipose tissue mitochondrial homeostasis during cold challenge
Lu, Y., Fujioka, H., Joshi, D., Li, Q., Sangwung, P., Hsieh, P., Zhu, J., Torio, J., Sweet, D., Wang, L., et al. (2018) · Scientific Reports · doi:10.1038/s41598-018-26394-5 · Cited by 76 · see citing works
Autophagy and mitophagy in the myocardium: therapeutic potential and concerns
Jimenez, R. E., Kubli, D. A., & Gustafsson, Å. B. (2013) · British Journal of Pharmacology · doi:10.1111/bph.12477 · Cited by 76 · see citing works
Triolo, M., Oliveira, A. N., Kumari, R., & Hood, D. A. (2022) · Skeletal Muscle · doi:10.1186/s13395-022-00296-7 · Cited by 75 · see citing works
“Furthermore, a lack of autophagy attenuates the phenotypic remodeling of muscle associated with exercise training [17–19].”
BackgroundTarget acquired: Selective autophagy in cardiometabolic disease
Evans, T. D., Sergin, I., Zhang, X., & Razani, B. (2017) · Science Signaling · doi:10.1126/scisignal.aag2298 · Cited by 73 · see citing works
Mitophagy in maintaining skeletal muscle mitochondrial proteostasis and metabolic health with ageing
Drake, J. C., & Yan, Z. (2017) · The Journal of Physiology · doi:10.1113/jp274337 · Cited by 74 · see citing works
Self-citationIrazoki, A., Martínez‐Vicente, M., Aparicio, P., Aris, C., Alibakhshi, E., Rubio-Valera, M., Castellanos, J., Lores, L., Palacı́n, M., Gumà, A., et al. (2022) · Aging Cell · doi:10.1111/acel.13583 · Cited by 73 · see citing works
Lieberman, D. E., Kistner, T. M., Richard, D. J., Lee, I.-M. M., & Baggish, A. L. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2107621118 · Cited by 73 · see citing works
Moderate Exercise Improves Experimental Cancer Cachexia by Modulating the Redox Homeostasis
Ballarò, R., Penna, F., Pin, F., Gómez-Cabrera, M., Viña, J., & Costelli, P. (2019) · Cancers · doi:10.3390/cancers11030285 · Cited by 65 · see citing works
Aoyama, S., Kim, H., Hirooka, R., Tanaka, M., Shimoda, T., Chijiki, H., Kojima, S., Sasaki, K., Takahashi, K., Makino, S., et al. (2019) · Cell Reports · doi:10.1016/j.celrep.2021.109336 · Cited by 73 · see citing works
Redox regulation of autophagy in skeletal muscle
Rodney, G. G., Pal, R., & Abo‐Zahrah, R. (2016) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2016.05.010 · Cited by 72 · see citing works
Autophagy in the Regulation of Tissue Differentiation and Homeostasis
Perrotta, C., Cattaneo, M. G., Molteni, R., & Palma, C. D. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.602901 · Cited by 72 · see citing works
Effects of aerobic training on markers of autophagy in the elderly
Mejías-Peña, Y., Rodriguez-Miguelez, P., Fernandez-Gonzalo, R., Martínez-Flórez, S., Almar, M., de Paz, J. A., Cuevas, M. J., & González-Gallego, J. (2016) · AGE · doi:10.1007/s11357-016-9897-y · Cited by 69 · see citing works
Muscle mitohormesis promotes cellular survival via serine/glycine pathway flux
Ost, M., Keipert, S., van Schothorst, E. M., Donner, V., van der Stelt, I., Kipp, A. P., Petzke, K., Jové, M., Pamplona, R., Portero‐Otín, M., et al. (2014) · The FASEB Journal · doi:10.1096/fj.14-261503 · Cited by 69 · see citing works
PGC-1α and exercise intensity dependent adaptations in mouse skeletal muscle
Brandt, N., Dethlefsen, M. M., Bangsbo, J., & Pilegaard, H. (2017) · PLoS ONE · doi:10.1371/journal.pone.0185993 · Cited by 68 · see citing works
Cui, D., Drake, J. C., Wilson, R. J., Shute, R. J., Lewellen, B. M., Zhang, M., Zhao, H., Sabik, O. L., Önengüt, S., Berr, S. S., et al. (2020) · The FASEB Journal · doi:10.1096/fj.201903055r · Cited by 67 · see citing works
Self-citation
- 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
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Medicine › Rehabilitation › 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
