{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T01:48:35Z","timestamp":1774489715938,"version":"3.50.1"},"reference-count":29,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,12,8]],"date-time":"2021-12-08T00:00:00Z","timestamp":1638921600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002426","name":"Telethon Foundation","doi-asserted-by":"publisher","award":["#20568"],"award-info":[{"award-number":["#20568"]}],"id":[{"id":"10.13039\/501100002426","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["PE-2016-02363049"],"award-info":[{"award-number":["PE-2016-02363049"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Skeletal muscle is a very dynamic and plastic tissue, being essential for posture, locomotion and respiratory movement. Muscle atrophy or genetic muscle disorders, such as muscular dystrophies, are characterized by myofiber degeneration and replacement with fibrotic tissue. Recent studies suggest that changes in muscle metabolism such as mitochondrial dysfunction and dysregulation of intracellular Ca2+ homeostasis are implicated in many adverse conditions affecting skeletal muscle. Accumulating evidence also suggests that ER stress may play an important part in the pathogenesis of inflammatory myopathies and genetic muscle disorders. Among the different known proteins regulating ER structure and function, we focused on RTN-1C, a member of the reticulon proteins family localized on the ER membrane. We previously demonstrated that RTN-1C expression modulates cytosolic calcium concentration and ER stress pathway. Moreover, we recently reported a role for the reticulon protein in autophagy regulation. In this study, we found that muscle differentiation process positively correlates with RTN-1C expression and UPR pathway up-regulation during myogenesis. To better characterize the role of the reticulon protein alongside myogenic and muscle regenerative processes, we performed in vivo experiments using either a model of muscle injury or a photogenic model for Duchenne muscular dystrophy. The obtained results revealed RTN-1C up-regulation in mice undergoing active regeneration and localization in the injured myofibers. The presented results strongly suggested that RTN-1C, as a protein involved in key aspects of muscle metabolism, may represent a new target to promote muscle regeneration and repair upon injury.<\/jats:p>","DOI":"10.3390\/metabo11120855","type":"journal-article","created":{"date-parts":[[2021,12,8]],"date-time":"2021-12-08T23:30:00Z","timestamp":1639006200000},"page":"855","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Reticulon-1C Involvement in Muscle Regeneration"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4313-8347","authenticated-orcid":false,"given":"Federica","family":"Rossin","sequence":"first","affiliation":[{"name":"Department of Biology, University of Rome \u2018Tor Vergata\u2019, 00133 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"Avitabile","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Rome \u2018Tor Vergata\u2019, 00133 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7513-145X","authenticated-orcid":false,"given":"Giorgia","family":"Catarinella","sequence":"additional","affiliation":[{"name":"Epigenetics and Regenerative Medicine, IRCCS Fondazione Santa Lucia, 00179 Rome, Italy"},{"name":"DAHFMO, Unit of Histology and Medical Embryology, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ersilia","family":"Fornetti","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Rome \u2018Tor Vergata\u2019, 00133 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefano","family":"Testa","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Rome \u2018Tor Vergata\u2019, 00133 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Serafina","family":"Oliverio","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Rome \u2018Tor Vergata\u2019, 00133 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1742-3969","authenticated-orcid":false,"given":"Cesare","family":"Gargioli","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Rome \u2018Tor Vergata\u2019, 00133 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefano","family":"Cannata","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Rome \u2018Tor Vergata\u2019, 00133 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucia","family":"Latella","sequence":"additional","affiliation":[{"name":"Epigenetics and Regenerative Medicine, IRCCS Fondazione Santa Lucia, 00179 Rome, Italy"},{"name":"Institute of Translational Pharmacology, National Research Council of Italy, 00133 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Federica","family":"Di Sano","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Rome \u2018Tor Vergata\u2019, 00133 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Sui, S.X., Williams, L.J., Holloway-Kew, K.L., Hyde, N.K., and Pasco, J.A. (2020). Skeletal Muscle Health and Cognitive Function: A Narrative Review. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22010255"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"8884283","DOI":"10.1155\/2021\/8884283","article-title":"Myogenic Differentiation of Stem Cells for Skeletal Muscle Regeneration","volume":"2021","author":"Yu","year":"2021","journal-title":"Stem Cells Int."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2582","DOI":"10.1242\/jeb.128348","article-title":"Prevention of muscle wasting and osteoporosis: The value of examining novel animal models","volume":"219","author":"Reilly","year":"2016","journal-title":"J. Exp. Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1007\/s00109-008-0373-8","article-title":"Nuclear factor-kappa B signaling in skeletal muscle atrophy","volume":"86","author":"Li","year":"2008","journal-title":"J. Mol. Med."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Yamakawa, H., Kusumoto, D., Hashimoto, H., and Yuasa, S. (2020). Stem Cell Aging in Skeletal Muscle Regeneration and Disease. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21051830"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1002\/jcp.25852","article-title":"Emerging roles of ER stress and unfolded protein response pathways in skeletal muscle health and disease","volume":"233","author":"Bohnert","year":"2018","journal-title":"J. Cell. Physiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1097\/JES.0b013e3182355e8c","article-title":"Endoplasmic reticulum stress in skeletal muscle: Origin and metabolic consequences","volume":"40","author":"Deldicque","year":"2012","journal-title":"Exerc. Sport Sci. Rev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1111\/febs.14358","article-title":"ER stress in skeletal muscle remodeling and myopathies","volume":"286","author":"Afroze","year":"2019","journal-title":"FEBS J."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1007\/s11926-012-0247-5","article-title":"Endoplasmic Reticulum Stress in Skeletal Muscle Homeostasis and Disease","volume":"14","author":"Rayavarapu","year":"2012","journal-title":"Curr. Rheumatol. Rep."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1038\/nrneurol.2017.99","article-title":"ER stress and the unfolded protein response in neurodegeneration","volume":"13","author":"Hetz","year":"2017","journal-title":"Nat. Rev. Neurol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Pant, M., Sopariwala, D.H., Bal, N.C., Lowe, J., Delf\u00edn, D.A., Rafael-Fortney, J., and Periasamy, M. (2015). Metabolic Dysfunction and Altered Mitochondrial Dynamics in the Utrophin-Dystrophin Deficient Mouse Model of Duchenne Muscular Dystrophy. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0123875"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1186\/gb-2007-8-12-234","article-title":"The reticulons: A family of proteins with diverse functions","volume":"8","author":"Yang","year":"2007","journal-title":"Genome Biol."},{"key":"ref_13","first-page":"3860","article-title":"Glucosylceramide synthase and its functional interaction with RTN-1C regulate chemotherapeutic-induced apoptosis in neuroepithelioma cells","volume":"63","author":"Fazi","year":"2003","journal-title":"Cancer Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1111\/j.1471-4159.2007.04479.x","article-title":"Reticulon-1C acts as a molecular switch between endoplasmic reticulum stress and genotoxic cell death pathway in human neuroblastoma cells","volume":"102","author":"Fazi","year":"2007","journal-title":"J. Neurochem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1016\/j.bbamcr.2014.12.031","article-title":"Reticulon protein-1C is a key component of MAMs","volume":"1853","author":"Reali","year":"2015","journal-title":"Biochim. Biophys. Acta Bioenerget."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1038\/s41419-019-2099-7","article-title":"Modulation of autophagy by RTN-1C: Role in autophagosome biogenesis","volume":"10","author":"Risuglia","year":"2019","journal-title":"Cell Death Dis."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1839","DOI":"10.1038\/cdd.2016.70","article-title":"Autophagy regulates satellite cell ability to regenerate normal and dystrophic muscles","volume":"23","author":"Fiacco","year":"2016","journal-title":"Cell Death Differ."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1038\/s41467-020-20123-1","article-title":"Mechanisms of muscle atrophy and hypertrophy: Implications in health and disease","volume":"12","author":"Sartori","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"9062","DOI":"10.1038\/s41598-018-27429-7","article-title":"Attenuation of autophagy impacts on muscle fibre development, starvation induced stress and fibre regeneration following acute injury","volume":"8","author":"Paolini","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e50863","DOI":"10.15252\/embr.202050863","article-title":"HDAC inhibitors tune miRNAs in extracellular vesicles of dystrophic muscle-resident mesenchymal cells","volume":"21","author":"Consalvi","year":"2020","journal-title":"EMBO Rep."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/j.cell.2005.05.010","article-title":"Stem Cell Function, Self-Renewal, and Behavioral Heterogeneity of Cells from the Adult Muscle Satellite Cell Niche","volume":"122","author":"Collins","year":"2005","journal-title":"Cell"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1038\/nrm3591","article-title":"Molecular regulation of stem cell quiescence","volume":"14","author":"Cheung","year":"2013","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.1038\/embor.2013.182","article-title":"Cellular dynamics in the muscle satellite cell niche","volume":"14","author":"Bentzinger","year":"2013","journal-title":"EMBO Rep."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"602901","DOI":"10.3389\/fcell.2020.602901","article-title":"Autophagy in the Regulation of Tissue Differentiation and Homeostasis","volume":"8","author":"Perrotta","year":"2020","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3639","DOI":"10.1242\/dev.067595","article-title":"An absolute requirement for Pax7-positive satellite cells in acute injury-induced skeletal muscle regeneration","volume":"138","author":"Lepper","year":"2011","journal-title":"Development"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1007\/s004410051054","article-title":"Neuronal differentiation is accompanied by NSP-C expression","volume":"292","author":"Hens","year":"1998","journal-title":"Cell Tissue Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1006\/geno.1997.5175","article-title":"cDNA Cloning, Genomic Organization, and Expression of the HumanRTN2Gene, a Member of a Gene Family Encoding Reticulons","volume":"51","author":"Roebroek","year":"1998","journal-title":"Genomics"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3814","DOI":"10.1038\/onc.2009.233","article-title":"Acetylation of RTN-1C regulates the induction of ER stress by the inhibition of HDAC activity in neuroectodermal tumors","volume":"28","author":"Fazi","year":"2009","journal-title":"Oncogene"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e201900437","DOI":"10.26508\/lsa.201900437","article-title":"Fibro-adipogenic pro-genitors of dystrophic mice are insensitive to NOTCH regulation of adipogenesis","volume":"2","author":"Marinkovic","year":"2019","journal-title":"Life Sci. Alliance"}],"container-title":["Metabolites"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-1989\/11\/12\/855\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:43:12Z","timestamp":1760168592000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-1989\/11\/12\/855"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,8]]},"references-count":29,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["metabo11120855"],"URL":"https:\/\/doi.org\/10.3390\/metabo11120855","relation":{},"ISSN":["2218-1989"],"issn-type":[{"value":"2218-1989","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,8]]}}}