Autophagy regulates cytoplasmic remodeling during cell reprogramming in a zebrafish model of muscle regeneration
Open accessAbstract
Cell identity involves both selective gene activity and specialization of cytoplasmic architecture and protein machinery. Similarly, reprogramming differentiated cells requires both genetic program alterations and remodeling of the cellular architecture. While changes in genetic and epigenetic programs have been well documented in dedifferentiating cells, the pathways responsible for remodeling the cellular architecture and eliminating specialized protein complexes are not as well understood. Here, we utilize a zebrafish model of adult muscle regeneration to study cytoplasmic remodeling during cell dedifferentiation. We describe activation of autophagy early in the regenerative response to muscle injury, while blocking autophagy using chloroquine or Atg5 and Becn1 knockdown reduced the rate of regeneration with accumulation of sarcomeric and nuclear debris. We further identify Casp3/caspase 3 as a candidate mediator of cellular reprogramming and Fgf signaling as an important activator of autophagy in dedifferentiating myocytes. We conclude that autophagy plays a critical role in cell reprogramming by regulating cytoplasmic remodeling, facilitating the transition to a less differentiated cell identity.
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ulk1 knockout impairs muscle regeneration in zebrafish.
“Similarly, ulk1 knockout impairs muscle regeneration in zebrafish [476],”
From Autophagy and ALS: mechanistic insights and therapeutic implications (2022) · cites this paper as [476]
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Cites
Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT Method
Livak, K. J., & Schmittgen, T. D. (2001) · Methods · doi:10.1006/meth.2001.1262 · Cited by 180,860 · see citing works
Takahashi, K., & Yamanaka, S. (2006) · Cell · doi:10.1016/j.cell.2006.07.024 · Cited by 26,673 · see citing works
Heart Regeneration in Zebrafish
Poss, K. D., Wilson, L. G., & Keating, M. T. (2002) · Science · doi:10.1126/science.1077857 · Cited by 1,938 · see citing works
A chemical method for fast and sensitive detection of DNA synthesis in vivo
Salic, A. N., & Mitchison, T. J. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0712168105 · Cited by 1,859 · see citing works
Tanida, I., Ueno, T., & Kominami, E. (2008) · Methods in Molecular Biology™ · doi:10.1007/978-1-59745-157-4_4 · Cited by 1,785 · see citing works
Inhibition of Macroautophagy Triggers Apoptosis
Boya, P., González‐Polo, R. A., Casares, N., Perfettini, J., Dessen, P., Larochette, N., Métivier, D., Meley, D., Souquère, S., Yoshimori, T., et al. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.3.1025-1040.2005 · Cited by 1,629 · see citing works
Autophagy in mammalian development and differentiation
Mizushima, N., & Levine, B. (2010) · Nature Cell Biology · doi:10.1038/ncb0910-823 · Cited by 1,555 · see citing works
Old, new and emerging functions of caspases
Shalini, S., Dorstyn, L., Dawar, S., & Kumar, S. (2015) · Cell Death & Differentiation · doi:10.1038/cdd.2014.216 · Cited by 1,267 · see citing works
Emerging regulation and functions of autophagy
Boya, P., Reggiori, F., & Codogno, P. (2013) · Nature Cell Biology · doi:10.1038/ncb2788 · Cited by 1,216 · see citing works
Autophagy inhibition enhances therapy-induced apoptosis in a Myc-induced model of lymphoma
Amaravadi, R. K., Yu, D., Lum, J. J., Bui, T., Christophorou, M. A., Evan, G. I., Thomas‐Tikhonenko, A., & Thompson, C. B. (2007) · Journal of Clinical Investigation · doi:10.1172/jci28833 · Cited by 1,136 · see citing works
Autophagy gone awry in neurodegenerative diseases
Wong, E. S. P., & Cuervo, A. M. (2010) · Nature Neuroscience · doi:10.1038/nn.2575 · Cited by 883 · see citing works
Protein Turnover Via Autophagy: Implications for Metabolism
Mizushima, N., & Klionsky, D. J. (2007) · Annual Review of Nutrition · doi:10.1146/annurev.nutr.27.061406.093749 · Cited by 793 · see citing works
Self-citationDedifferentiation, transdifferentiation and reprogramming: three routes to regeneration
Jopling, C., Boué, S., & Belmonte, J. C. I. (2011) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3043 · Cited by 724 · see citing works
Mechanisms underlying differential responses to FGF signaling.
Dailey, L., Ambrosetti, D., Mansukhani, A., & Basilico, C. (2005) · Cytokine & growth factor reviews · doi:10.1016/j.cytogfr.2005.01.007 · Cited by 701 · see citing works
Autophagy mediates degradation of nuclear lamina
Dou, Z., Xu, C., Donahue, G., Shimi, T., Pan, J.-A., Zhu, J., Ivanov, A., Capell, B. C., Drake, A. M., Shah, P. P., et al. (2015) · Nature · doi:10.1038/nature15548 · Cited by 655 · see citing works
Müller glial cell reprogramming and retina regeneration
Goldman, D. J. (2014) · Nature reviews. Neuroscience · doi:10.1038/nrn3723 · Cited by 629 · see citing works
Receptor-mediated selective autophagy degrades the endoplasmic reticulum and the nucleus
Mochida, K., Oikawa, Y., Kimura, Y., Kirisako, H., Hirano, H., Ohsumi, Y., & Nakatogawa, H. (2015) · Nature · doi:10.1038/nature14506 · Cited by 611 · see citing works
The CASBAH: a searchable database of caspase substrates
Lüthi, A. U., & Martin, S. J. (2007) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4402103 · Cited by 434 · see citing works
Higashijima, S., Okamoto, H., Ueno, N., Hotta, Y., & Eguchi, G. (1997) · Developmental Biology · doi:10.1006/dbio.1997.8779 · Cited by 417 · see citing works
Ramachandran, R., Fausett, B. V., & Goldman, D. J. (2010) · Nature Cell Biology · doi:10.1038/ncb2115 · Cited by 361 · see citing works
Activation of Notch signaling pathway precedes heart regeneration in zebrafish
Raya, Á., Koth, C. M., Büscher, D., Kawakami, Y., Itoh, T., Raya, R. M., Sternik, G., Tsai, H., Rodrı́guez-Esteban, C., & Izpisúa‐Belmonte, J. C. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1834204100 · Cited by 341 · see citing works
Fgf signaling instructs position-dependent growth rate during zebrafish fin regeneration
Lee, Y., Grill, S., Sanchez, A., Murphy‐Ryan, M., & Poss, K. D. (2005) · Development · doi:10.1242/dev.02101 · Cited by 340 · see citing works
Roles for Fgf Signaling during Zebrafish Fin Regeneration
Poss, K. D., Shen, J., Nechiporuk, A. V., McMahon, G., Thisse, B., Thisse, C., & Keating, M. T. (2000) · Developmental Biology · doi:10.1006/dbio.2000.9722 · Cited by 332 · see citing works
A role for FGF-6 in skeletal muscle regenerationPreprint
Floß, T., Arnold, H.-H., & Braun, T. W. (1997) · Genes & Development · doi:10.1101/gad.11.16.2040 · Cited by 328 · see citing works
Müller glia: Stem cells for generation and regeneration of retinal neurons in teleost fish
Lenkowski, J. R., & Raymond, P. A. (2014) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2013.12.007 · Cited by 322 · see citing works
Dual roles of autophagy in the survival of <i>Caenorhabditis elegans</i> during starvation
Kang, C., You, Y.-J., & Avery, L. (2007) · Genes & Development · doi:10.1101/gad.1573107 · Cited by 294 · see citing works
In vivo cardiac reprogramming contributes to zebrafish heart regeneration
Zhang, R., Han, P., Yang, H., Ouyang, K., Lee, D. P. H., Lin, Y.-F., Ocorr, K. A., Kang, G., Chen, J., Stainier, D. Y. R., et al. (2013) · Nature · doi:10.1038/nature12322 · Cited by 260 · see citing works
Highly Coordinated Proteome Dynamics during Reprogramming of Somatic Cells to Pluripotency
Hansson, J., Rafiee, M., Reiland, S., Polo, J. M., Gehring, J. S., Okawa, S., Huber, W. K., Hochedlinger, K., & Krijgsveld, J. (2012) · Cell Reports · doi:10.1016/j.celrep.2012.10.014 · Cited by 238 · see citing works
The art of fin regeneration in zebrafish
Pfefferli, C., & Jaźwińska, A. (2015) · Regeneration · doi:10.1002/reg2.33 · Cited by 231 · see citing works
Corcelle–Termeau, E., Djerbi, N., Mari, M., Nebout, M., Fiorini, C., Fénichel, P., Hofman, P. M., Poujeol, P., & Mograbi, B. (2007) · Autophagy · doi:10.4161/auto.3424 · Cited by 184 · see citing works
Assaying autophagic activity in transgenic GFP-Lc3 and GFP-Gabarap zebrafish embryos
He, C., Bartholomew, C. R., Zhou, W., & Klionsky, D. J. (2009) · Autophagy · doi:10.4161/auto.5.4.7768 · Cited by 181 · see citing works
Self-citationAutophagic control of cell ‘stemness’
Pan, H., Cai, N., Li, M., Liu, G., & Belmonte, J. C. I. (2013) · EMBO Molecular Medicine · doi:10.1002/emmm.201201999 · Cited by 151 · see citing works
Thummel, R., Bai, S., Sarras, M. P., Song, P., McDermott, J. P., Brewer, J., Perry, M., Zhang, X., Hyde, D. R., & Godwin, A. R. F. (2005) · Developmental Dynamics · doi:10.1002/dvdy.20630 · Cited by 144 · see citing works
Caspase-8 Promotes Cell Motility and Calpain Activity under Nonapoptotic Conditions
Helfer, B. M., Boswell, B. C., Finlay, D., Ciprés, A., Vuori, K., Kang, T., Wallach, D., Dorfleutner, A., Lahti, J. M., Flynn, D. C., et al. (2006) · Cancer Research · doi:10.1158/0008-5472.can-05-4183 · Cited by 129 · 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
Beyond apoptosis: caspase regulatory mechanisms and functions in vivo
Kuranaga, E. (2012) · Genes to Cells · doi:10.1111/j.1365-2443.2011.01579.x · Cited by 111 · see citing works
The Teleost Retina as a Model for Developmental and Regeneration Biology
Hitchcock, P. F., & Raymond, P. A. (2004) · Zebrafish · doi:10.1089/zeb.2004.1.257 · Cited by 101 · see citing works
Fibroblast growth factor signaling in embryonic and cancer stem cells
Dvořák, P., Dvořáková, D., & Hampl, A. (2006) · FEBS Letters · doi:10.1016/j.febslet.2006.01.095 · Cited by 96 · see citing works
FADD-deficient T Cells Exhibit a Disaccord in Regulation of the Cell Cycle Machinery
Zhang, J., Kabra, N. H., Cado, D., Kang, C., & Winoto, A. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m103838200 · Cited by 86 · see citing works
The autophagy conundrum in cancer: influence of tumorigenic metabolic reprogramming
Eng, C. H., & Abraham, R. T. (2011) · Oncogene · doi:10.1038/onc.2011.220 · Cited by 81 · see citing works
Autophagy is required for zebrafish caudal fin regeneration
Varga, M., Sass, M., Papp, D., Takács‐Vellai, K., Kobolák, J., Dinnyés, A., Klionsky, D. J., & Vellai, T. (2013) · Cell Death and Differentiation · doi:10.1038/cdd.2013.175 · Cited by 78 · see citing works
Self-citationAutophagy and cell reprogramming
Wang, S., Xia, P., Rehm, M., & Fan, Z. (2015) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-014-1829-3 · Cited by 66 · see citing works
Expression pattern and functions of autophagy-related geneatg5in zebrafish organogenesis
Hu, Z., Zhang, J., & Zhang, Q. (2011) · Autophagy · doi:10.4161/auto.7.12.18040 · Cited by 65 · see citing works
Craig, S. E. L., Thummel, R., Ahmed, H., Vasta, G. R., Hyde, D. R., & Hitchcock, P. F. (2010) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.09-4879 · Cited by 64 · see citing works
Contribution of Caspase(s) to the Cell Cycle Regulation at Mitotic Phase
Hashimoto, T., Kikkawa, U., & Kamada, S. (2011) · PLoS ONE · doi:10.1371/journal.pone.0018449 · Cited by 50 · see citing works
Cellular reprogramming and cancer development
Semi, K., Matsuda, Y., Ohnishi, K., & Yamada, Y. (2013) · International Journal of Cancer · doi:10.1002/ijc.27963 · Cited by 46 · see citing works
Skeletal muscle regeneration in Xenopus tadpoles and zebrafish larvae
Rodrigues, A. M. C., Christen, B., Martí, M., & Belmonte, J. C. I. (2012) · BMC Developmental Biology · doi:10.1186/1471-213x-12-9 · Cited by 45 · see citing works
Fgf regulates dedifferentiation during skeletal muscle regeneration in adult zebrafish
Saera-Vila, A., Kish, P. E., & Kahana, A. (2016) · Cellular Signalling · doi:10.1016/j.cellsig.2016.06.001 · Cited by 45 · see citing works
Self-citationMyocyte Dedifferentiation Drives Extraocular Muscle Regeneration in Adult Zebrafish
Saera-Vila, A., Kasprick, D. S., Junttila, T. L., Grzegorski, S. J., Louie, K. W., Chiari, E. F., Kish, P. E., & Kahana, A. (2015) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.14-16103 · Cited by 35 · see citing works
Self-citationFrost, V. J., Al-Mehairi, S. S., & Sinclair, A. J. (2001) · Oncogene · doi:10.1038/sj.onc.1204367 · Cited by 29 · see citing works
Gurdon, J. B. (2009) · Nature Medicine · doi:10.1038/nm1009-1141 · Cited by 17 · see citing works
Automated Scalable Heat Shock Modification for Standard Aquatic Housing Systems
Saera-Vila, A., Kish, P. E., & Kahana, A. (2015) · Zebrafish · doi:10.1089/zeb.2015.1087 · Cited by 6 · see citing works
Self-citationCho, A., & Noguchi, S. (2013) · InTech eBooks · doi:10.5772/55223 · Cited by 4 · see citing works
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Autophagy and ALS: mechanistic insights and therapeutic implications
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“Similarly, ulk1 knockout impairs muscle regeneration in zebrafish [476], and conditional Atg7 deletion in mouse skeletal muscle leads to atrophy, weakness, and accumulation of unhealthy mitochondria and sarcoplasmic reticulum [477].”
BackgroundAutophagy in animal development
Allen, E. A., & Baehrecke, E. H. (2020) · Cell Death & Differentiation · doi:10.1038/s41418-020-0497-0 · Cited by 127 · see citing works
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Cai, Z., Liu, D., Yang, Y., Xie, W., He, M., Yu, D., Wu, Y., Wang, X., Xiao, W., & Li, Y. (2022) · Stem Cell Research & Therapy · doi:10.1186/s13287-022-02706-5 · Cited by 58 · see citing works
- Authors
- Saera-Vila, A., Kish, P. E., Louie, K. W., Grzegorski, S. J., Klionsky, D. J., & Kahana, A.
- Affiliations
- University of Michigan (US)
- Corresponding author
- Kahana, Alon
- Venue
- Autophagy
- Publisher
- Informa UK Limited
- Published
- 2016-09-14
- Volume
- 12
- Issue
- 10
- Pages
- 1864-1875
- ISSN
- 1554-8627 (ISSN-L)
- 1554-8635
- PMC
- PMC5066936
- OpenAlex
- W2502770985
- Cited by
- 69
- References
- 53
- Citations by year
- 2026: 4 · 2025: 13 · 2024: 4 · 2023: 4 · 2022: 7 · 2021: 10 · 2020: 9 · 2019: 4 · 2018: 9 · 2017: 4 · 2016: 1
- FWCI
- 5.63
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Autophagy (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Figshare (submittedVersion, cc-by)
- Figshare (cc-by)
- Funders
- National Eye Institute (R01EY022633, P30EY007003)
- National Cancer Institute (P30CA046592)
- National Institute of General Medical Sciences (R01GM053396)
- National Institute of Dental and Craniofacial Research (T32DE007057)
- National Center for Research Resources (P40RR012546)
- Topics
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- cellular reprogramming, muscle regeneration, dedifferentiation, caspase-3, FGF signaling, nuclear debris, ATG5, Beclin-1, chloroquine, zebrafish
- MeSH terms
- Animals, Autophagy, Cytoplasm, Energy Metabolism, Fibroblast Growth Factors, Models, Biological, Oculomotor Muscles, Regeneration, Zebrafish, Up-Regulation, Apoptosis, Cellular Reprogramming
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