AMPK Activation Stimulates Autophagy and Ameliorates Muscular Dystrophy in the mdx Mouse Diaphragm
Open accessAbstract
Duchenne muscular dystrophy (DMD) is characterized by myofiber death from apoptosis or necrosis, leading in many patients to fatal respiratory muscle weakness. Among other pathological features, DMD muscles show severely deranged metabolic gene regulation and mitochondrial dysfunction. Defective mitochondria not only cause energetic deficiency, but also play roles in promoting myofiber atrophy and injury via opening of the mitochondrial permeability transition pore. Autophagy is a bulk degradative mechanism that serves to augment energy production and eliminate defective mitochondria (mitophagy). We hypothesized that pharmacological activation of AMP-activated protein kinase (AMPK), a master metabolic sensor in cells and on-switch for the autophagy-mitophagy pathway, would be beneficial in the mdx mouse model of DMD. Treatment of mdx mice for 4 weeks with an established AMPK agonist, AICAR (5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside), potently triggered autophagy in the mdx diaphragm without inducing muscle fiber atrophy. In AICAR-treated mdx mice, the exaggerated sensitivity of mdx diaphragm mitochondria to calcium-induced permeability transition pore opening was restored to normal levels. There were associated improvements in mdx diaphragm histopathology and in maximal force-generating capacity, which were not linked to increased mitochondrial biogenesis or up-regulated utrophin expression. These findings suggest that agonists of AMPK and other inducers of the autophagy-mitophagy pathway can help to promote the elimination of defective mitochondria and may thus serve as useful therapeutic agents in DMD.
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Autophagy flux reactivation by dietary or pharmacological tools, like rapamycin, cyclosporine A, or AICAR, rescues the dystrophic phenotype by clearing the abnormal mitochondria.
“Importantly, autophagy flux reactivation by dietary or pharmacological tools, like rapamycin, cyclosporine A, or AICAR, rescues the dystrophic phenotype by clearing the abnormal mitochondria [243–246].”
From The connection between the dynamic remodeling of the mitochondrial network and the regulation of muscle mass (2021) · cites this paper as [246]
Enhancing autophagy in mouse models of Duchenne muscular dystrophy pharmacologically with rapamycin or AICAR improves muscle strength and contractility.
“In contrast, enhancing autophagy in mouse models of Duchenne muscular dystrophy (DMD) pharmacologically with rapamycin or 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR, an AMP analog which stimulates AMPK) improves muscle strength and contractility [480,481].”
From Autophagy and ALS: mechanistic insights and therapeutic implications (2022) · cites this paper as [481]
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BackgroundTurn up the power - pharmacological activation of mitochondrial biogenesis in mouse models
Komen, J. C., & Thorburn, D. R. (2014) · British Journal of Pharmacology · doi:10.1111/bph.12413 · Cited by 149 · see citing works
“Contrariwise, data from this study suggested that AICAR caused increased mitophagy in the diaphragm of mdx mice (Pauly et al., 2012).”
BackgroundResultInfluentialWasting Mechanisms in Muscular Dystrophy
Shin, J., Tajrishi, M. M., Ogura, Y., & Kumar, A. (2013) · International Journal of Biochemistry and Cell Biology · doi:10.1016/j.biocel.2013.05.001 · Cited by 146 · see citing works
Autophagy regulates satellite cell ability to regenerate normal and dystrophic muscles
Fiacco, E., Castagnetti, F., Bianconi, V., Madaro, L., Bardi, M. D., Nazio, F., D’Amico, A., Bertini, E., Cecconi, F., Puri, P., et al. (2016) · Cell Death and Differentiation · doi:10.1038/cdd.2016.70 · Cited by 147 · see citing works
Hughes, M. C., Ramos, S. V., Turnbull, P. C., Rebalka, I. A., Cao, A. W., Monaco, C. M. F., Varah, N. E., Edgett, B. A., Huber, J. S., Tadi, P., et al. (2019) · Journal of Cachexia Sarcopenia and Muscle · doi:10.1002/jcsm.12405 · Cited by 133 · see citing works
“been implicated in DMD myopathy in response to calcium stress.(8,51) However, the synergistic link with mH2O2 had not been demonstrated.”
BackgroundResultMyricanol rescues dexamethasone-induced muscle dysfunction Via a sirtuin 1-dependent mechanism
Shen, S., Liao, Q., Liu, J., Pan, R., Lee, S. M., & Lin, L. (2019) · Journal of Cachexia Sarcopenia and Muscle · doi:10.1002/jcsm.12393 · Cited by 142 · see citing works
“Notably, AMPK activator, such as AICAR (5-aminoimidazole-4-carboxamide ribonucleotide), has been reported to clean the damaged mitochondria through activating autophagy, resulting in improved dystrophic phenotype in diaphragm atrophy.(57) Interestingly, MY increased the phosphorylated AMPK level in C2C12 myotubes, and…”
BackgroundDu, L., Chai, D., Zhao, L., Li, X.-H., Zhang, F.-C., Zhang, H., Liu, L.-B., Wu, K., Liu, R., Wang, J., et al. (2014) · Journal of Alzheimer s Disease · doi:10.3233/jad-140564 · Cited by 138 · see citing works
“By recycling components of damaged mitochondria, mitophagy may be as important in maintaining a healthy cellular ATP-generating capacity as promoting the elimination of defective mitochondria and the production of new mitochondria [43, 44].”
microRNA-378 promotes autophagy and inhibits apoptosis in skeletal muscle
Li, Y., Jiang, J., Liu, W., Wang, H., Zhao, L., Liu, S., Li, P., Zhang, S., Sun, C., Wu, Y., et al. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1803377115 · Cited by 134 · see citing works
“In agreement with the notion that muscular dystrophy exhibits defective autophagy and excessive apoptosis (35, 36), we found that the levels of lipidated LC3 were decreased while the levels of cleaved PARP were increased in muscle biopsy specimens from DMD patients compared with those from normal subjects (SI Appendix…”
Timpani, C. A., Hayes, A., & Rybalka, E. (2015) · Medical Hypotheses · doi:10.1016/j.mehy.2015.08.015 · Cited by 133 · see citing works
“As it has been recently demonstrated thatmdxmitochondria hypersensitively respond to a Ca load to prematurely open the permeability transition pore (channel that initiates mitochondrial death) [110], we suggest that the inability of dystrophic mitochondria to respond to an overwhelming Ca stimulus by ramping up ATP pr…”
BackgroundInfluentialCoupling of mitochondrial function and skeletal muscle fiber type by a miR‐499/Fnip1/AMPK circuit
Liu, J., Liang, X., Zhou, D., Lai, L., Xiao, L., Liu, L., Fu, T., Kong, Y., Zhou, Q., Vega, R. B., et al. (2016) · EMBO Molecular Medicine · doi:10.15252/emmm.201606372 · Cited by 129 · see citing works
“Recent work has linked defects in mitophagy to mdx muscular dystrophy (Pauly et al, 2012), and it is also possible that miR-499 enhance muscle function by promoting the clearance of defective mitochondria.”
Song, J., Liu, J., Cui, C., Hu, H., Zang, N., Yang, M., Yang, J., Zou, Y., Li, J., Wang, L., et al. (2023) · Journal of Cachexia, Sarcopenia and Muscle · doi:10.1002/jcsm.13177 · Cited by 118 · see citing works
“Deletion of AMPK from skeletal muscle dramatically reduces the exercise capacity of mice,(19) whereas AMPK activation ameliorates muscle dystrophy.(20) AMPK is also an important intracellular energy sensor regulating metabolic homeostasis,(21) which is crucial for maintaining skeletal muscle function.”
BackgroundIschemic conditioning-induced endogenous brain protection: Applications pre-, per- or post-stroke
Wang, Y., Reis, C., Applegate, R. L., Stier, G. R., Martin, R., & Zhang, J. H. (2015) · Experimental Neurology · doi:10.1016/j.expneurol.2015.04.009 · Cited by 113 · see citing works
“…is debatable and uncertain (Wei et al., 2012), though previous studies have pointed out AMPK’s ability to provide cerebroprotection against ischemia in peripheral organs (Matsui et al., 2007; Nepal and Park, 2013; Pauly et al., 2012; Wang et al., 2013a; Xie et al., 2011; Zaouali et al., 2013).”
BackgroundThe fine tuning of metabolism, autophagy and differentiation during in vitro myogenesis
Fortini, P., Ferretti, C., Iorio, E., Cagnin, M., Garribba, L., Pietraforte, D., Falchi, M., Pascucci, B., Baccarini, S., Morani, F., et al. (2016) · Cell Death and Disease · doi:10.1038/cddis.2016.50 · Cited by 110 · see citing works
“at baseline level may represent an adaptive response to the presence of mitochondrial damage and energetic stress.(45) In response, AMPk would promote catabolic pathways to generate more ATP in agreement with the switch to glycolysis and increased ATP levels observed in p53 null cells.”
BackgroundGuo, A., Li, K., Tian, H., Fan, Z., Chen, Q., Yang, Y., Yu, J., Wu, Y., & Xiao, Q. (2021) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.16448 · Cited by 112 · see citing works
Jiang, T., Yu, J., Zhu, X., Zhang, Q.-Q., Tan, M., Cao, L., Wang, H.-F., Shi, J., Gao, L., Qin, H., et al. (2014) · Molecular Neurobiology · doi:10.1007/s12035-014-8725-6 · Cited by 107 · see citing works
Shen, Y., Ye, B., Chen, P., Wang, Q., Fan, C., Shu, Y., & Xiang, M. (2018) · Frontiers in Neuroscience · doi:10.3389/fnins.2018.00394 · Cited by 105 · see citing works
Augmenting Autophagy to Treat Acute Kidney Injury during Endotoxemia in Mice
Howell, G. M., Gomez, H., Collage, R. D., Loughran, P., Zhang, X., Escobar, D. A., Billiar, T. R., Zuckerbraun, B. S., & Rosengart, M. R. (2013) · PLoS ONE · doi:10.1371/journal.pone.0069520 · Cited by 105 · see citing works
“Young mice receiving AICAR 24 hours prior to CLP had significantly lower cystatin (280 vs. 635 ng/mL, p = 0.02) concentrations at 48 hours, compared with animals that received diluent control prior to CLP (Fig.”
MethodInfluentialMitochondrial Dysfunction Is an Early Consequence of Partial or Complete Dystrophin Loss in mdx Mice
Moore, T. M., Lin, A. J., Strumwasser, A. R., Cory, K., Whitney, K. A., Ho, T., Ho, T., Lee, J. L., Rucker, D. H., Nguyen, C. Q., et al. (2020) · Frontiers in Physiology · doi:10.3389/fphys.2020.00690 · Cited by 103 · see citing works
“Evidence links muscular dystrophies with mitochondrial and metabolic dysfunction (Lucas-Héron et al., 1990; Kemp et al., 1993; Even et al., 1994; Mokhtarian et al., 1996; Sperl et al., 1997; Kuznetsov et al., 1998; McIntosh et al., 1998a; Cole et al., 2002; Angelin et al., 2007; Khairallah et al., 2007; Gulston et al.…”
BackgroundPride, C. K., Mo, L., Quesnelle, K., Dagda, R. K., Murillo, D., Geary, L., Corey, C., Portella, R., Zharikov, S., St Croix, C., et al. (2014) · Cardiovascular Research · doi:10.1093/cvr/cvt224 · Cited by 97 · see citing works
“Cardiovascular Research (2014) 101, 57–68 doi:10.1093/cvr/cvt224 D ow nloaded from https://academ ic.oup.com /cardiovascres/article-abstract/101/1/57/273151 by guest on 08 M arch 2019 sub-lethal ischaemia,16,17 volatile anaesthetics,18 and adenosine.19 For example, the inhibition of ATP production and the incremental…”
InfluentialModulating Mitophagy in Mitochondrial Disease
Dombi, E., Mortiboys, H., & Poulton, J. (2017) · Current Medicinal Chemistry · doi:10.2174/0929867324666170616101741 · Cited by 99 · see citing works
Ljubicic, V., Burt, M., Lunde, J. A., & Jasmin, B. J. (2014) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00357.2013 · Cited by 93 · see citing works
“Chronic stimulation of the phenotypic modifier AMPK with the pharmacologic agonist 5-aminoimidazole-4-carboxamide-1- -D-ribofuranoside (AICAR) elicited numerous favorable adaptations in dystrophic muscle in the absence of any alterations in utrophin A expression (48).”
InfluentialHall, D. T., Griss, T., Ma, J. F., Sanchez, B. J., Sadek, J., Tremblay, A. M. K., Mubaid, S., Omer, A., Ford, R. J., Bedard, N., et al. (2018) · EMBO Molecular Medicine · doi:10.15252/emmm.201708307 · Cited by 88 · see citing works
“Indeed, the therapeutic potential of AMPK activation is further unscored by the fact that AMPK activation can protect muscle in mdx mice (a model of Duchenne’s Muscular Dystrophy) and in Angiotensisin II-driven muscle atrophy (Tabony et al, 2011; Pauly et al, 2012).”
BackgroundTargeting deregulated AMPK/mTORC1 pathways improves muscle function in myotonic dystrophy type I
Brockhoff, M., Rion, N., Chojnowska, K., Wiktorowicz, T., Eickhorst, C., Erne, B., Frank, S., Angelini, C. I., Furling, D., Rüegg, M. A., et al. (2017) · Journal of Clinical Investigation · doi:10.1172/jci89616 · Cited by 88 · see citing works
“As no myotonia was detected in the slow, soleus muscle of HSALR mice and as AICAR and rapamycin were previously shown to alter muscle fiber types (42, 43), we tested whether changes in muscle function upon treatments were related to modification of muscle metabolic and contractile capacities.”
BackgroundOxidative Stress‐Mediated Skeletal Muscle Degeneration: Molecules, Mechanisms, and Therapies
Choi, M. H., Ow, J. R., Yang, N.-D., & Taneja, R. (2015) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2016/6842568 · 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
“Additionally, stimulation of autophagy (a cellular process essential for degradation of dysfunctional and/or damaged organelles) in the mdx mouse decreased the presence of dysfunctional mitochondria and was associated with an improvement in muscle function (24).”
BackgroundBibee, K. P., Cheng, Y., Ching, J. K., Marsh, J. N., Li, A. J., Keeling, R. M., Connolly, A. M., Golumbek, P. T., Myerson, J. W., Hu, G., et al. (2014) · The FASEB Journal · doi:10.1096/fj.13-237388 · Cited by 83 · 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
“report that autophagy stimulation via AMPK agonist administration ameliorates dystrophic features in Dmd diaphragms.(48) Rapamycin (an autophagy activator via MTOR blockade) also significantly improves the dystrophic phenotype.”
BackgroundThe role of αB-crystallin in skeletal and cardiac muscle tissues
Dimauro, I., Antonioni, A., Mercatelli, N., & Caporossi, D. (2017) · Cell Stress and Chaperones · doi:10.1007/s12192-017-0866-x · Cited by 81 · see citing works
“Therefore, another possible strategy might be to further stimulate autophagy using one among numerous compounds already described in the literature (e.g., AMPK, cyclosporine A, rapamycin) (Pauly et al. 2012; Rubinsztein et al. 2012).”
Hafner, P., Bonati, U., Erne, B., Schmid, M., Rubino, D., Pohlman, U., Peters, T. T. A., Rutz, E., Frank, S., Neuhaus, C., et al. (2016) · PLoS ONE · doi:10.1371/journal.pone.0147634 · Cited by 80 · see citing works
“Chronic AMPK stimulation triggers beneficial adaptations [20] and ameliorates the dystrophic phenotype in the mdx mouse model [21].”
BackgroundLjubicic, V., Burt, M., & Jasmin, B. J. (2013) · The FASEB Journal · doi:10.1096/fj.13-238071 · Cited by 79 · see citing works
“Petrof’s group (144) postulated that pharmacologic stimulation of AMPK would be therapeutic in dystrophic muscle via activation of autophagy signaling.”
BackgroundCall, 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
“Specifically, existing evidence suggests that stimulating autophagy in Duchenne muscular dystrophy promotes functional recovery; however, it is unclear if autophagy is activated and required for functional recovery after muscle injury (11, 35).”
BackgroundMitochondrial Dysfunction in Neuromuscular Disorders
Katsetos, C. D., Koutzaki, S. H., & Melvin, J. J. (2013) · Seminars in Pediatric Neurology · doi:10.1016/j.spen.2013.10.010 · Cited by 75 · see citing works
Garbincius, J. F., & Michele, D. E. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1512991112 · Cited by 71 · see citing works
“Chronic activation of AMPKwith administration of the AMP analog 5-aminoimidazole-4-carboxamide riboside (AICAR) (47) in mdx mice has been shown to promote a slow oxidative muscle phenotype, increase utrophin expression, and enhance sarcolemmal stability in skeletal muscle (48), and to reduce ongoing muscle damage and…”
BackgroundMuscle ERRγ mitigates Duchenne muscular dystrophy via metabolic and angiogenic reprogramming
Matsakas, A., Yadav, V., Lorca, S., & Narkar, V. A. (2013) · The FASEB Journal · doi:10.1096/fj.13-228296 · Cited by 71 · see citing works
“AMPK, an upstream activator of PGC1 (49) as well as PPAR (50), has also been reported to ameliorate DMD by evoking the slow oxidative myogenic program and/or by stimulating autophagy (7, 8).”
BackgroundPalma, C. D., Perrotta, C., Pellegrino, P., Clementi, E., & Cervia, D. (2014) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2014.00188 · Cited by 66 · see citing works
Metabolic reprogramming of fibro/adipogenic progenitors facilitates muscle regeneration
Reggio, A., Rosina, M., Krahmer, N., Palma, A., Petrilli, L. L., Maiolatesi, G., Massacci, G., Salvatori, I., Valle, C., Testa, S., et al. (2020) · Life Science Alliance · doi:10.26508/lsa.202000660 · Cited by 62 · see citing works
“Here, we show that in a mouse model of DMD (mdx), fibro/ adipogenic progenitors (FAPs) are characterized by a dysfunctional mitochondrial metabolism which correlates with increased adipogenic potential.”
BackgroundInfluentialInhibition of autophagy promoted high glucose/ROS-mediated apoptosis in ADSCs
Li, Q., Yin, Y., Zheng, Y., Chen, F., & Jin, P. (2018) · Stem Cell Research & Therapy · doi:10.1186/s13287-018-1029-4 · Cited by 64 · see citing works
Mitochondrial dynamics in exercise physiology
Tanaka, T., Nishimura, A., Nishiyama, K., Goto, T., Numaga‐Tomita, T., & Nishida, M. (2019) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-019-02258-3 · Cited by 66 · see citing works
Basse, A. L., Agerholm, M., Farup, J., Dalbram, E., Nielsen, J., Ørtenblad, N., Altıntaş, A., Ehrlich, A. M., Krag, T. O. B., Bruzzone, S., et al. (2021) · Molecular Metabolism · doi:10.1016/j.molmet.2021.101271 · Cited by 62 · see citing works
“Increased AMPK phosphorylation has also been observed in mdx mice [81].”
BackgroundSatellite cell contribution to disease pathology in Duchenne muscular dystrophy
Kodippili, K., & Rudnicki, M. A. (2023) · Frontiers in Physiology · doi:10.3389/fphys.2023.1180980 · Cited by 61 · see citing works
“And restoring mitochondrial bioenergetic function ameliorated the DMD pathology in mouse models (Pauly et al., 2012; Luan et al., 2021).”
BackgroundFu, X., Zhao, J., Zhu, M. J., Foretz, M., Viollet, B., Dodson, M. V., & Du, . (2013) · Molecular and Cellular Biology · doi:10.1128/mcb.01078-13 · Cited by 60 · see citing works
“The role of AMPK in muscle fiber atrophy has been well defined; a number of studies demonstrated that AMPK promotes muscle protein degradation and autophagy (17) and inhibits protein synthesis (18).”
BackgroundMournetas, V., Massouridès, E., Dupont, J., Kornobis, É., Polvèche, H., Jarrige, M., Dorval, A. R. L., Gosselin, M. R. F., Manousopoulou, A., Garbis, S. D., et al. (2021) · Journal of Cachexia Sarcopenia and Muscle · doi:10.1002/jcsm.12665 · Cited by 60 · see citing works
“mPTP is a multiprotein complex whose members are not all precisely identified, and several studies suggest that it might be involved in DMD pathophysiology.(79,80) A chicken-and-egg”
Deficit in PINK1/PARKIN-mediated mitochondrial autophagy at late stages of dystrophic cardiomyopathy
Kang, C., Badr, M. A., Kyrychenko, V., Eskelinen, E., & Shirokova, N. (2017) · Cardiovascular Research · doi:10.1093/cvr/cvx201 · Cited by 60 · see citing works
Camerino, G. M., Cannone, M., Giustino, A., Massari, A. M., Capogrosso, R. F., Cozzoli, A., & Luca, A. D. (2014) · Human Molecular Genetics · doi:10.1093/hmg/ddu287 · Cited by 58 · see citing works
“Restoring autophagy by a low-protein diet or by pharmacological stimulation of AMPK by AICAR has been found toameliorate themdxphenotype, althoughadefectiveadaptation has also been described (25,39,55).”
BackgroundHollinger, K., Gardan‐Salmon, D., Santana, C., Rice, D., Snella, E. M., & Selsby, J. T. (2013) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00221.2012 · Cited by 57 · see citing works
“Given recent findings using a similar, but distinct, approach (43), we also measured expression of genes related to autophagy.”
BackgroundResultXiao, Y., Ma, C., Yi, J., Wu, S., Guo, L., Xu, X., Lin, P., Sun, J., & Zhou, J. (2015) · Physiological Reports · doi:10.14814/phy2.12271 · Cited by 56 · see citing works
“Moreover, recent studies have found autophagy dysregulation in muscular dystrophies (Grumati et al. 2010; Pauly et al. 2012).”
BackgroundSegatto, M., Szokoll, R., Fittipaldi, R., Bottino, C., Nevi, L., Mamchaoui, K., Filippakopoulos, P., & Caretti, G. (2020) · Nature Communications · doi:10.1038/s41467-020-19839-x · Cited by 56 · see citing works
Manifestations of Age on Autophagy, Mitophagy and Lysosomes in Skeletal Muscle
Triolo, M., & Hood, D. A. (2021) · Cells · doi:10.3390/cells10051054 · Cited by 57 · see citing works
Yang, S., Long, L., Li, D., Zhang, J., Jin, S., Wang, F., & Chen, J. (2015) · Aging Cell · doi:10.1111/acel.12371 · Cited by 55 · see citing works
Mantuano, P., Sanarica, F., Conte, E., Morgese, M. G., Capogrosso, R. F., Cozzoli, A., Fonzino, A., Quaranta, A., Rolland, J., Bellis, M. D., et al. (2018) · Biochemical Pharmacology · doi:10.1016/j.bcp.2018.04.022 · Cited by 55 · see citing works
The Roles and Pharmacological Effects of FGF21 in Preventing Aging-Associated Metabolic Diseases
Yan, J., Nie, Y., Cao, J., Luo, M., Yan, M., Chen, Z., & He, B. (2021) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2021.655575 · Cited by 53 · see citing works
“FGF21 could improve muscular dystrophy and atrophy through metabolic pathways (55, 56).”
BackgroundKerr, H. L., Krumm, K., Anderson, B., Christiani, A. J., Strait‐Bodey, L., Li, T., Irwin, B., Jiang, S., Rybachok, A., Chen, A. L., et al. (2024) · Journal of Clinical Investigation · doi:10.1172/jci172890 · Cited by 54 · see citing works
“For instance, proteins such as C1QA, C1QC, CO8B, FIBA, and FIBB, restore mitochondrial function by activating autophagy via ULK1 to remove damaged mitochondria and reduce mitochondrial oxidative stress (27, 73).”
Self-citationThe Impact of Mitochondrial Deficiencies in Neuromuscular Diseases
Cantó, J., Grau‐Junyent, J. M., & Garrabou, G. (2020) · Antioxidants · doi:10.3390/antiox9100964 · Cited by 53 · see citing works
Al-Rewashdy, H., Ljubicic, V., Lin, W., Renaud, J., & Jasmin, B. J. (2014) · Human Molecular Genetics · doi:10.1093/hmg/ddu535 · Cited by 52 · see citing works
Ljubicic, V., & Jasmin, B. J. (2013) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2013.07.002 · Cited by 51 · see citing works
Skeletal Muscle Metabolism in Duchenne and Becker Muscular Dystrophy—Implications for Therapies
Heydemann, A. (2018) · Nutrients · doi:10.3390/nu10060796 · Cited by 43 · see citing works
“Data also indicates that there is a natural—probably compensatory—increase of pAMPK levels in mdx mice [45].”
BackgroundInfluentialValladares-Ide, D., Utreras‐Mendoza, Y., Campos, C., Morales, C., Díaz‐Vegas, A., Contreras‐Ferrat, A. E., Westermeier, F., Jaimovich, E., Marchi, S., Pinton, P., et al. (2018) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2018.08.042 · Cited by 51 · see citing works
Panda, P. K., Fahrner, A., Vats, S., Seranova, E., Sharma, V., Chipara, M., Desai, P., Torresi, J., Rosenstock, T., Kumar, D., et al. (2019) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2019.00038 · Cited by 50 · see citing works
“A potential role of simvastatin, which has been reported to induce autophagy by inhibiting the Rac1-mTOR pathway (Wei et al., 2013), has been suggested in improving the physiological function of skeletal muscle in DMD transgenic mice (Whitehead et al., 2015).”
BackgroundInfluentialCastets, P., Frank, S., Sinnreich, M., & Rüegg, M. A. (2016) · Journal of Neuromuscular Diseases · doi:10.3233/jnd-160153 · Cited by 49 · see citing works
“increasing mitochondria integrity and autophagic flux [168].”
Hughes, M. C., Ramos, S. V., Turnbull, P. C., Edgett, B. A., Huber, J. S., Polidovitch, N., Schlattner, U., Backx, P. H., Simpson, J. A., & Perry, C. G. R. (2019) · The Journal of Physiology · doi:10.1113/jp277306 · Cited by 42 · see citing works
“Such PTP formation has also already been implicated in DMD myopathy in response to calcium stress (Godin et al. 2012; Pauly et al. 2012).”
BackgroundThe Interplay of Mitophagy and Inflammation in Duchenne Muscular Dystrophy
Reid, A. L., & Alexander, M. S. (2021) · Life · doi:10.3390/life11070648 · Cited by 48 · see citing works
“AMPK activation via the treatment with AMPK agonist AICAR in mdx mice improved mitophagy, reduced ROS levels and upregulated PGC-1α and utrophin expression, resulting in the improvement of muscle function and histological pathology markers [56,59,73].”
BackgroundRelationship between Autophagy and Ventilator-induced Diaphragmatic Dysfunction
Azuelos, I., Jung, B., Picard, M. A., Liang, F., Li, T., Lemaire, C. F., Giordano, C., Hussain, S. N. A., & Petrof, B. J. (2015) · Anesthesiology · doi:10.1097/aln.0000000000000656 · Cited by 47 · see citing works
Self-citationMyofibrillar Myopathies: New Perspectives from Animal Models to Potential Therapeutic Approaches
Batonnet‐Pichon, S., Béhin, A., Cabet, É., Delort, F., Vicart, P., & Lilienbaum, A. (2017) · Journal of Neuromuscular Diseases · doi:10.3233/jnd-160203 · Cited by 46 · see citing works
“Although some of these drugs have been successfully tested in animal models of muscular dystrophy [89, 90], they have not yet been tried in MFM models.”
BackgroundModulating Metabolism to Improve Cancer‐Induced Muscle Wasting
Penna, F., Ballarò, R., Beltrà, M., Lucia, S. D., & Costelli, P. (2018) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2018/7153610 · Cited by 46 · see citing works
“This drug also revealed able to activate autophagy and to improve muscle phenotype in both dystrophic mdx mice and animals bearing the C26 tumor [16, 90] .”
BackgroundAMP-Activated Protein Kinase as a Key Trigger for the Disuse-Induced Skeletal Muscle Remodeling
Vilchinskaya, N. A., Krivoi, I. I., & Shenkman, B. S. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19113558 · Cited by 45 · see citing works
“of Duchenne muscular dystrophy, suggesting AMPK as a powerful therapeutic target [129,130].”
BackgroundGiovarelli, M., Zecchini, S., Catarinella, G., Moscheni, C., Sartori, P., Barbieri, C., Roux-Biejat, P., Napoli, A., Vantaggiato, C., Cervia, D., et al. (2021) · Pharmacological Research · doi:10.1016/j.phrs.2021.105751 · Cited by 45 · see citing works
Hulmi, J. J., Oliveira, B. M. S., Silvennoinen, M., Hoogaars, W. M. H., Pasternack, A. H., Kainulainen, H., & Ritvos, O. (2013) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00065.2013 · Cited by 45 · see citing works
“Recent evidence suggests that autophagy is needed to maintain muscle mass in some catabolic states (39) and that induction of autophagy can rescue mdx and some other forms of muscle dystrophies (12, 17, 47).”
BackgroundShared and Distinct Mechanisms of Skeletal Muscle Atrophy: A Narrative Review
Wilburn, D. T., Ismaeel, A., Machek, S. B., Fletcher, E., & Koutakis, P. (2021) · Ageing Research Reviews · doi:10.1016/j.arr.2021.101463 · Cited by 44 · see citing works
Autophagy is Impaired in the Tibialis Anterior of Dystrophin Null Mice
Spitali, P., Grumati, P., Hiller, M., Chrisam, M., Aartsma-Rus, A. M., & Bonaldo, P. (2013) · PLoS Currents · doi:10.1371/currents.md.e1226cefa851a2f079bbc406c0a21e80 · Cited by 43 · see citing works
ER stress disturbs SR/ER-mitochondria Ca2+ transfer: Implications in Duchenne muscular dystrophy
Pauly, M., Angebault, C., Dridi, H., Notarnicola, C., Scheuermann, V., Lacampagne, A., Matecki, S., & Fauconnier, J. (2017) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2017.06.009 · Cited by 44 · see citing works
Self-citationAutophagy: an essential but limited cellular process for timely skeletal muscle recovery from injury
Call, J. A., & Nichenko, A. S. (2020) · Autophagy · doi:10.1080/15548627.2020.1753000 · Cited by 45 · see citing works
“With further stimutation of autophagy using the AMP-activated protein kinase (AMPK) agonist AICAR, the result was an increase in skeletal muscle contractility and mitochondrial content in dmd mice [6].”
MethodSoundharrajan, I., Kim, D., Srigopalram, S., Arasu, M. V., Lee, K., Lee, J. W., Lee, J., Senthil, R., & Choi, K. C. (2016) · Molecules · doi:10.3390/molecules21080997 · Cited by 43 · see citing works
The Role of AMPK in Neuromuscular Biology and Disease
Dial, A. G., Ng, S. Y., Manta, A., & Ljubicic, V. (2018) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2018.02.010 · Cited by 43 · see citing works
Is Exercise the Right Medicine for Dystrophic Muscle?
Spaulding, H. R., & Selsby, J. T. (2018) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0000000000001639 · Cited by 43 · see citing works
Lambert, O., Poussard, S., Décossas, M., Bihan, O. L., Mornet, S., & Naudin, G. (2015) · International Journal of Nanomedicine · doi:10.2147/ijn.s74158 · Cited by 43 · see citing works
“targeting defective autophagy have been observed in mdx mice.(18) Notably, rapamycin, an autophagy-inducing compound successfully delivered using nanoparticle formulation, enhanced physical performance.”
- Authors
- Pauly, M., Daussin, F., Burelle, Y., Li, T., Godin, R., Fauconnier, J., Koechlin-Ramonatxo, C., Hugon, G., Lacampagne, A., Coisy-Quivy, M., Liang, F., Hussain, S., Matecki, S., & Petrof, B. J.
- Affiliations
- Inserm (FR)
- Université de Montréal (CA)
- McGill University Health Centre (CA)
- Corresponding author
- Petrof, Basil J.
- Venue
- The American Journal of Pathology
- Publisher
- Elsevier BV
- Published
- 2012-08
- Volume
- 181
- Issue
- 2
- Pages
- 583-592
- ISSN
- 0002-9440 (ISSN-L)
- OpenAlex
- W2169836157
- Cited by
- 225
- References
- 50
- Citations by year
- 2026: 6 · 2025: 9 · 2024: 10 · 2023: 19 · 2022: 9 · 2021: 19 · 2020: 16 · 2019: 9 · 2018: 28 · 2017: 20 · 2016: 18 · 2015: 15 · 2014: 22 · 2013: 23 · 2012: 2
- FWCI
- 7.94
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- American Journal Of Pathology (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion, other-oa)
- Funders
- Canadian Institutes of Health Research
- Association Française contre les Myopathies
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- Duchenne muscular dystrophy, AMPK, AICAR, autophagy, mitophagy, mdx mice, diaphragm, mitochondrial permeability transition pore, mitochondrial dysfunction, respiratory muscle weakness, muscle fiber atrophy, utrophin
- MeSH terms
- Mechanistic Target of Rapamycin Complex 1, Mitochondrial Permeability Transition Pore, Aminoimidazole Carboxamide, Animals, Autophagy, Diaphragm, Energy Metabolism, Enzyme Activation, Male, Mice, Inbred C57BL, Mitochondria, Muscle Contraction, Muscular Dystrophy, Animal, Oxidation-Reduction, Proteins, Ribonucleotides, Signal Transduction, Mice, Inbred mdx, Mitochondrial Membrane Transport Proteins, Multiprotein Complexes, Mice, AMP-Activated Protein Kinases, TOR Serine-Threonine Kinases, In Vitro Techniques
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