Ampk phosphorylation of Ulk1 is required for targeting of mitochondria to lysosomes in exercise-induced mitophagy
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Mitochondrial health is critical for skeletal muscle function and is improved by exercise training through both mitochondrial biogenesis and removal of damaged/dysfunctional mitochondria via mitophagy. The mechanisms underlying exercise-induced mitophagy have not been fully elucidated. Here, we show that acute treadmill running in mice causes mitochondrial oxidative stress at 3-12 h and mitophagy at 6 h post-exercise in skeletal muscle. These changes were monitored using a novel fluorescent reporter gene, pMitoTimer, that allows assessment of mitochondrial oxidative stress and mitophagy in vivo, and were preceded by increased phosphorylation of AMP activated protein kinase (Ampk) at tyrosine 172 and of unc-51 like autophagy activating kinase 1 (Ulk1) at serine 555. Using mice expressing dominant negative and constitutively active Ampk in skeletal muscle, we demonstrate that Ulk1 activation is dependent on Ampk. Furthermore, exercise-induced metabolic adaptation requires Ulk1. These findings provide direct evidence of exercise-induced mitophagy and demonstrate the importance of Ampk-Ulk1 signaling in skeletal muscle.Exercise is associated with biogenesis and removal of dysfunctional mitochondria. Here the authors use a mitochondrial reporter gene to demonstrate the occurrence of mitophagy following exercise in mice, and show this is dependent on AMPK and ULK1 signaling.
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Physical activity stimulates mitophagy.
“was recently shown to stimulate mitophagy [57,153,167,168]”
From Mitochondrial Dynamics and Mitophagy in Skeletal Muscle Health and Aging (2021) · cites this paper as [167]
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Cites
Repertoires 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
How mitochondria produce reactive oxygen species
Murphy, M. P. (2009) · Biochemical Journal · doi:10.1042/bj20081386 · Cited by 8,207 · see citing works
AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1
Kim, J., Kundu, M., Viollet, B., & Guan, K.-L. (2011) · Nature Cell Biology · doi:10.1038/ncb2152 · Cited by 7,227 · see citing works
Self-citationSuppression of basal autophagy in neural cells causes neurodegenerative disease in mice
Hara, T., Nakamura, K., Matsui, M., Yamamoto, A., Nakahara, Y., Suzuki-Migishima, R., Yokoyama, M., Mishima, K., Saito, I., Okano, H., et al. (2006) · Nature · doi:10.1038/nature04724 · Cited by 3,882 · see citing works
Mutation of the mouse klotho gene leads to a syndrome resembling ageing
Kuro-o, M., Matsumura, Y., Aizawa, H., Kawaguchi, H., Suga, T., Utsugi, T., Ohyama, Y., Kurabayashi, M., Kaname, T., Kume, E., et al. (1997) · Nature · doi:10.1038/36285 · Cited by 3,837 · see citing works
PINK1/Parkin-mediated mitophagy is dependent on VDAC1 and p62/SQSTM1
Geisler, S., Holmström, K. M., Skujat, D., Fiesel, F. C., Rothfuss, O. C., Kahle, P. J., & Springer, W. (2010) · Nature Cell Biology · doi:10.1038/ncb2012 · Cited by 2,835 · see citing works
Boveris, A., & Chance, B. (1973) · Biochemical Journal · doi:10.1042/bj1340707 · Cited by 2,626 · see citing works
Phosphorylation of ULK1 (hATG1) by AMP-Activated Protein Kinase Connects Energy Sensing to Mitophagy
Egan, D. F., Shackelford, D. B., Mihaylova, M. M., Gelino, S., Kohnz, R. A., Mair, W., Vasquez, D. S., Joshi, A., Gwinn, D. M., Taylor, R., et al. (2011) · Science · doi:10.1126/science.1196371 · Cited by 2,600 · see citing works
Self-citationHow to Interpret LC3 Immunoblotting
Mizushima, N., & Yoshimori, T. (2007) · Autophagy · doi:10.4161/auto.4600 · Cited by 2,595 · see citing works
Endoplasmic reticulum stress: cell life and death decisions
Xu, C. (2005) · Journal of Clinical Investigation · doi:10.1172/jci26373 · Cited by 2,260 · see citing works
Free radicals and tissue damage produced by exercise
Davies, K. J. A., Quintanilha, A. T., Brooks, G. A., & Packer, L. (1982) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(82)80124-1 · Cited by 1,739 · 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
Biochemical Adaptations in Muscle
Holloszy, J. O. (1967) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)96046-1 · Cited by 1,517 · see citing works
Mitochondrial membrane potential regulates PINK1 import and proteolytic destabilization by PARL
Jin, S. M., Lazarou, M., Wang, C., Kane, L. A., Narendra, D. P., & Youle, R. J. (2010) · Journal of Cell Biology · doi:10.1083/jcb.201008084 · Cited by 1,375 · see citing works
PINK1-Phosphorylated Mitofusin 2 Is a Parkin Receptor for Culling Damaged Mitochondria
Chen, Y., & Dorn, G. W. (2013) · Science · doi:10.1126/science.1231031 · Cited by 1,323 · see citing works
Nix is a selective autophagy receptor for mitochondrial clearance
Novak, I., Kirkin, V., McEwan, D. G., Zhang, J., Wild, P., Rozenknop, A., Rogov, V., Löhr, F., Popovic, D., Occhipinti, A., et al. (2010) · The EMBO Reports · doi:10.1038/embor.2009.256 · Cited by 1,309 · see citing works
Mitotic phosphorylation of dynamin-related GTPase Drp1 participates in mitochondrial fission.
Taguchi, N., Ishihara, N., Jofuku, A., Oka, T., & Mihara, K. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m607279200 · Cited by 1,226 · 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
Dephosphorylation by calcineurin regulates translocation of Drp1 to mitochondria
Cereghetti, G. M., Stangherlin, A., de Brito, O. M., Chang, C. R., Blackstone, C., Bernardi, P., & Scorrano, L. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0808249105 · Cited by 1,129 · see citing works
AMP-activated protein kinase mediates mitochondrial fission in response to energy stress
Toyama, E. Q., Herzig, S., Courchet, J., Lewis, T. L., Losón, O. C., Hellberg, K., Young, N. P., Chen, H., Polleux, F., Chan, D. C., et al. (2016) · Science · doi:10.1126/science.aab4138 · Cited by 1,085 · see citing works
Cribbs, J. T., & Strack, S. (2007) · EMBO Reports · doi:10.1038/sj.embor.7401062 · Cited by 1,024 · see citing works
Rogov, V., Dötsch, V., Johansen, T., & Kirkin, V. (2014) · Molecular Cell · doi:10.1016/j.molcel.2013.12.014 · Cited by 992 · see citing works
Winder, W. W., & Hardie, D. G. (1996) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1996.270.2.e299 · Cited by 799 · see citing works
Chang, C., & Blackstone, C. D. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.c700083200 · Cited by 792 · see citing works
Kundu, M., Lindsten, T., Yang, C.-Y., Wu, J., Zhao, F., Zhang, J., Selak, M. A., Ney, P. A., & Thompson, C. B. (2008) · Blood · doi:10.1182/blood-2008-02-137398 · Cited by 571 · see citing works
Self-citationLiu, Z., & Roche, P. A. (2015) · Frontiers in Physiology · doi:10.3389/fphys.2015.00001 · Cited by 560 · see citing works
Shang, L., Chen, S., Du, F., Shen, L., Zhao, L., & Wang, X. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1100844108 · Cited by 540 · see citing works
The Association of AMPK with ULK1 Regulates Autophagy
Lee, J. W., Park, S., Takahashi, Y., & Wang, H.-G. (2010) · PLoS ONE · doi:10.1371/journal.pone.0015394 · Cited by 482 · see citing works
Mitochondrial 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
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
Self-citationHoffman, N. J., Parker, B. L., Chaudhuri, R., Fisher-Wellman, K. H., Kleinert, M., Humphrey, S. J., Yang, P., Holliday, M., Trefely, S., Fazakerley, D. J., et al. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.09.001 · Cited by 426 · see citing works
Huntingtin functions as a scaffold for selective macroautophagy
Rui, Y.-N., Xu, Z., Patel, B., Chen, Z., Chen, D., Tito, A., David, G., Sun, Y., Stimming, E. F., Bellen, H. J., et al. (2015) · Nature Cell Biology · doi:10.1038/ncb3101 · Cited by 423 · see citing works
CaM kinase Iα–induced phosphorylation of Drp1 regulates mitochondrial morphology
Han, X.-J., Lü, Y.-F., Li, S.-A., Kaitsuka, T., Sato, Y., Tomizawa, K., Nairn, A. C., Takei, K., Matsui, H., & Matsushita, M. (2008) · The Journal of Cell Biology · doi:10.1083/jcb.200802164 · Cited by 423 · 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-citationO'Neill, H. M., Maarbjerg, S. J., Crane, J. D., Jeppesen, J., Jørgensen, S. B., Schertzer, J. D., Shyroka, O., Kiens, B., van Denderen, B. J., Tarnopolsky, M. A., et al. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1105062108 · Cited by 406 · see citing works
"Fluorescent Timer": Protein That Changes Color with Time
Terskikh, A. V., Fradkov, A. F., Алексеевна, Е. Г., Zaraisky, A. G., Tan, P. B. O., Kajava, A. V., Zhao, X., Lukyanov, S., Matz, M. V., Kim, S. K., et al. (2000) · Science · doi:10.1126/science.290.5496.1585 · Cited by 402 · see citing works
Contraction-induced Changes in Acetyl-CoA Carboxylase and 5′-AMP-activated Kinase in Skeletal Muscle
Vavvas, D., Apazidis, A., Saha, A. K., Gamble, J., Patel, A., Kemp, B. E., Witters, L. A., & Ruderman, N. B. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.20.13255 · Cited by 395 · 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-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
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
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-citationA Novel MitoTimer Reporter Gene for Mitochondrial Content, Structure, Stress, and Damage in Vivo
Laker, R. C., Xu, P., Ryall, K. A., Sujkowski, A. L., Kenwood, B. M., Chain, K. H., Zhang, M., Royal, M. A., Hoehn, K. L., Driscoll, M., et al. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.530527 · Cited by 254 · see citing works
Self-citationThe serine/threonine kinase ULK1 is a target of multiple phosphorylation events
Bach, M., Larance, M., James, D. E., & Ramm, G. (2011) · Biochemical Journal · doi:10.1042/bj20101894 · Cited by 253 · see citing works
AMPK Activation of Muscle Autophagy Prevents Fasting-Induced Hypoglycemia and Myopathy during Aging
Bujak, A. L., Crane, J. D., Lally, J., Ford, R. J., Kang, S. J., Rebalka, I. A., Green, A. E., Kemp, B. E., Hawke, T. J., Schertzer, J. D., et al. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.05.016 · Cited by 252 · see citing works
PGC-1α-mediated adaptations in skeletal muscle
Olesen, J., Kiilerich, K., & Pilegaard, H. (2010) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-010-0834-0 · Cited by 244 · see citing works
Exercise Training-Induced Regulation of Mitochondrial Quality
Yan, Z., Lira, V. A., & Greene, N. P. (2012) · Exercise and Sport Sciences Reviews · doi:10.1097/jes.0b013e3182575599 · Cited by 233 · see citing works
Self-citationLimmathurotsakul, D., Jamsen, K. M., Arayawichanont, A., et al. (2010) · PLoS ONE · doi:10.1371/journal.pone.0012485 · Cited by 225 · see citing works
Signaling mechanisms in skeletal muscle: acute responses and chronic adaptations to exercise
Röckl, K. S. C., Witczak, C. A., & Goodyear, L. J. (2008) · IUBMB Life · doi:10.1002/iub.21 · Cited by 222 · see citing works
Self-citationMitochondria in Exercise-Induced Oxidative Stress
Meo, S. D., & Venditti, P. (2001) · Neurosignals · doi:10.1159/000046880 · Cited by 214 · see citing works
Phosphorylation of ULK1 by AMPK regulates translocation of ULK1 to mitochondria and mitophagy
Tian, W., Li, W., Chen, Y., Yan, Z., Huang, X., Zhuang, H., Zhong, W., Chen, Y., Wu, W., Lin, C., et al. (2015) · FEBS Letters · doi:10.1016/j.febslet.2015.05.020 · Cited by 199 · see citing works
Self-citationLi, J., Wang, Y., Wang, Y., Wen, X., Ma, X., Chen, W., Huang, F., Kou, J., Qi, L., Liu, B., et al. (2015) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2015.07.010 · Cited by 182 · see citing works
Fujii, N., Hirshman, M. F., Kane, E. M., Ho, R. C., Peter, L. E., Seifert, M. M., & Goodyear, L. J. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m504208200 · Cited by 177 · see citing works
Self-citationAMPK governs lineage specification through Tfeb-dependent regulation of lysosomesPreprint
Young, N. P., Kamireddy, A., Nostrand, J. L. V., Eichner, L. J., Shokhirev, M. N., Dayn, Y., & Shaw, R. J. (2016) · Genes & Development · doi:10.1101/gad.274142.115 · Cited by 177 · 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
Yun, H., Park, S., Kim, M., Yang, W. K., Im, D. U., Yang, K. R., Hong, J., Choe, W., Kang, I., Kim, S. S., et al. (2014) · FEBS Journal · doi:10.1111/febs.12949 · Cited by 171 · see citing works
Wu, S., Wu, Y., Wu, T.-P., & Wei, Y. (2013) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2013.10.034 · Cited by 159 · 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
AMPK‐independent pathways regulate skeletal muscle fatty acid oxidation
Dzamko, N., Schertzer, J. D., Ryall, J. G., Steel, R., Macaulay, S. L., Wee, S., Chen, Z., Michell, B. J., Oakhill, J. S., Watt, M. J., et al. (2008) · The Journal of Physiology · doi:10.1113/jphysiol.2008.159814 · Cited by 147 · see citing works
Holloszy, J. O., Tseng, B. S., Marsh, D. R., Hamilton, M. T., & Booth, F. W. (1995) · The Journals of Gerontology Series A · doi:10.1093/gerona/50a.special_issue.113 · Cited by 147 · 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
Scheele, C. C., Petrovič, N., Faghihi, M. A., Lassmann, T., Fredriksson, K., Rooyackers, O., Wahlestedt, C., Good, L., & Timmons, J. A. (2007) · BMC Genomics · doi:10.1186/1471-2164-8-74 · Cited by 137 · 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
AMPK Regulates ER Morphology and Function in Stressed Pancreatic β-Cells via Phosphorylation of DRP1
Wikström, J. D., Israeli, T., Bachar-Wikström, E., Swisa, A., Ariav, Y., Waiss, M., Kaganovich, D., Dor, Y., Cerasi, E., & Leibowitz, G. (2013) · Molecular Endocrinology · doi:10.1210/me.2013-1109 · Cited by 119 · 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
Ai, H., Ihlemann, J., Hellsten, Y., Lauritzen, H. P. M. M., Hardie, D. G., Galbo, H., & Ploug, T. (2002) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00167.2001 · Cited by 103 · see citing works
DNA Transfection of Mammalian Skeletal Muscles using In Vivo Electroporation
DiFranco, M., Quiñonez, M., Capote, J. C., & Vergara, J. L. (2009) · Journal of Visualized Experiments · doi:10.3791/1520 · Cited by 101 · see citing works
Autophagy and Protein Turnover Signaling in Slow-Twitch Muscle during Exercise
PAGANO, A. F., PY, G., BERNARDI, H., CANDAU, R. B., & SANCHEZ, A. M. J. (2014) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0000000000000237 · Cited by 96 · see citing works
Green, H. J., Thomson, J. A., Daub, W. D., Houston, M. E., & Ranney, D. (1979) · European Journal of Applied Physiology · doi:10.1007/bf00421658 · Cited by 88 · see citing works
Barré, L. K., Richardson, C., Hirshman, M. F., Brozinick, J. T., Fiering, S., Kemp, B. E., Goodyear, L. J., & Witters, L. A. (2006) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00369.2006 · Cited by 72 · see citing works
Self-citationLefort, N., St.-Amand, E., Morasse, S., Côté, C. H., & Marette, A. (2008) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.90362.2008 · Cited by 57 · see citing works
Chronology of UPR activation in skeletal muscle adaptations to chronic contractile activity
Memme, J. M., Oliveira, A. N., & Hood, D. A. (2016) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00009.2016 · Cited by 55 · see citing works
Effect of stimulation frequency on contraction-induced glucose transport in rat skeletal muscle
Ihlemann, J., Ploug, T., Hellsten, Y., & Galbo, H. (2000) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.2000.279.4.e862 · Cited by 53 · see citing works
Endurance training in mice increases the unfolded protein response induced by a high-fat diet
Deldicque, L., Cani, P. D., Delzenne, N. M., Baar, K., & Francaux, M. (2013) · Journal of Physiology and Biochemistry · doi:10.1007/s13105-012-0204-9 · Cited by 41 · see citing works
Role of AMPK in skeletal muscle gene adaptation in relation to exercise
Jørgensen, S. B., Jensen, T. E., & Richter, E. A. (2007) · Applied Physiology, Nutrition, and Metabolism · doi:10.1139/h07-079 · Cited by 32 · see citing works
Role of mitochondria in exercise-induced oxidative stress in skeletal muscle from hyperthyroid rats
Venditti, P., Bari, A., Stefano, L. D., & Meo, S. D. (2007) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2007.02.004 · Cited by 27 · see citing works
Chen, S., Zhu, P., Guo, H.-M., Solis, R. S., Wang, Y., Ma, Y., Wang, J., Gao, J., Chen, J., Ge, Y., et al. (2014) · Life Sciences · doi:10.1016/j.lfs.2014.01.006 · Cited by 26 · see citing works
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Klionsky, D. J., Abdel-Aziz, A. K., Abdelfatah, S., Abdellatif, M., Abdoli, A., Abel, S., Abeliovich, H., Abildgaard, M. H., Abudu, Y. P., Acevedo-Arozena, A., et al. (2021) · Autophagy · doi:10.1080/15548627.2020.1797280 · Cited by 2,622 · see citing works
Self-citationMitophagy in human health, ageing and disease
Picca, A., Faitg, J., Auwerx, J., Ferrucci, L., & D’Amico, D. (2023) · Nature Metabolism · doi:10.1038/s42255-023-00930-8 · Cited by 635 · see citing works
Andreux, P. A., Blanco-Bose, W., Ryu, D., Burdet, F., Ibberson, M., Aebischer, P., Auwerx, J., Singh, A., & Rinsch, C. (2019) · Nature Metabolism · doi:10.1038/s42255-019-0073-4 · Cited by 590 · 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
Mitophagy: An Emerging Role in Aging and Age-Associated Diseases
Chen, G., Kroemer, G., & Kepp, O. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.00200 · Cited by 359 · 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
Exercise Metabolism and Adaptation in Skeletal Muscle
Smith, J. A. B., Murach, K. A., Dyar, K. A., & Zierath, J. R. (2023) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-023-00606-x · Cited by 342 · see citing works
Mitochondrial Dynamics and Mitophagy in Skeletal Muscle Health and Aging
Leduc-Gaudet, J.-P., Hussain, S. N. A., Barreiro, E., & Gouspillou, G. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22158179 · Cited by 268 · see citing works
“Interestingly, physical activity, which is well known to improve muscle and mitochondrial health in the elderly [166], was recently shown to stimulate mitophagy [57,153,167,168] and increase Parkin expression in the skeletal muscles of rodents [153] and humans [57,168].”
BackgroundCarter, 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
Exercise and mitochondrial dynamics: keeping in shape with ROS and AMPK
Trewin, A., Berry, B., & Wojtovich, A. (2018) · Antioxidants · doi:10.3390/antiox7010007 · Cited by 129 · see citing works
Physical Exercise: A Novel Tool to Protect Mitochondrial Health
Sorriento, D., Di Vaia, E., & Iaccarino, G. (2021) · Frontiers in Physiology · doi:10.3389/fphys.2021.660068 · Cited by 118 · see citing works
Inhibition of autophagy curtails visual loss in a model of autosomal dominant optic atrophy
Zaninello, M., Palikaras, K., Naon, D., Iwata, K., Herkenne, S., Quintana-Cabrera, R., Semenzato, M., Grespi, F., Ross-Cisneros, F. N., Carelli, V., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-17821-1 · Cited by 92 · see citing works
Alternative polyadenylation of Pax3 controls muscle stem cell fate and muscle function
de Morree, A., Klein, J. D. D., Gan, Q., Farup, J., Urtasun, A., Kanugovi, A., Bilen, B., van Velthoven, C. T. J., Quarta, M., & Rando, T. A. (2019) · Science · doi:10.1126/science.aax1694 · Cited by 81 · see citing works
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Handy, R. M., & Holloway, G. P. (2023) · Frontiers in Physiology · doi:10.3389/fphys.2023.1151389 · Cited by 38 · see citing works
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Liang, J., Zeng, Z., Zhang, Y., & Chen, N. (2020) · Experimental Gerontology · doi:10.1016/j.exger.2019.110789 · Cited by 33 · see citing works
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Wang, J., Jia, D., Zhang, Z., & Wang, D. (2025) · Metabolites · doi:10.3390/metabo15010059 · Cited by 23 · see citing works
Yang, Y., Ke, J., Cao, Y., Gao, Y., & Lin, C. (2024) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2024.117092 · Cited by 17 · see citing works
- Authors
- 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., Kundu, M., & Yan, Z.
- Affiliations
- University of Virginia Medical Center (US)
- University of Iowa (US)
- University of Virginia (US)
- Brigham and Women's Hospital (US)
- St. Jude Children's Research Hospital (US)
- Corresponding author
- Yan, Zhen
- ORCID
- Venue
- Nature Communications
- Published
- 2017-09-15
- Volume
- 8
- Issue
- 1
- Pages
- 548-548
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC5601463
- OpenAlex
- W2754409876
- Cited by
- 529
- References
- 76
- Citations by year
- 2026: 71 · 2025: 53 · 2024: 64 · 2023: 82 · 2022: 65 · 2021: 66 · 2020: 54 · 2019: 38 · 2018: 30 · 2017: 6
- FWCI
- 27.42
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- American Heart Association (14POST20450061, 114PRE20380254)
- Joslin Diabetes Center (5P30 DK36836)
- National Institutes of Health (HL007284, DK101043, DK 36836)
- National Heart, Lung, and Blood Institute (R01HL114697, T32HL007284)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK101043, P30DK036836)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR050429)
- Topics
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Keywords
- mitophagy, exercise training, AMPK, ULK1, mitochondrial oxidative stress, skeletal muscle, mitochondrial biogenesis, autophagy, metabolic adaptation, treadmill running
- MeSH terms
- Autophagy-Related Protein-1 Homolog, Animals, Humans, Lysosomes, Male, Mice, Inbred C57BL, Mitochondria, Phosphorylation, Exercise, Oxidative Stress, Muscle, Skeletal, Amino Acid Motifs, Mice, AMP-Activated Protein Kinases, Mitophagy
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