{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T01:15:05Z","timestamp":1779930905328,"version":"3.53.1"},"reference-count":50,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2022,6,8]],"date-time":"2022-06-08T00:00:00Z","timestamp":1654646400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Instituto de Salud Carlos III (ISCIII)","award":["PI17\/01067"],"award-info":[{"award-number":["PI17\/01067"]}]},{"name":"the Instituto de Salud Carlos III (ISCIII)","award":["PI18\/0049"],"award-info":[{"award-number":["PI18\/0049"]}]},{"name":"the Instituto de Salud Carlos III (ISCIII)","award":["PI21\/00935"],"award-info":[{"award-number":["PI21\/00935"]}]},{"name":"the Instituto de Salud Carlos III (ISCIII)","award":["PI21\/01085"],"award-info":[{"award-number":["PI21\/01085"]}]},{"name":"the Instituto de Salud Carlos III (ISCIII)","award":["PI20\/0448"],"award-info":[{"award-number":["PI20\/0448"]}]},{"name":"the Instituto de Salud Carlos III (ISCIII)","award":["2017SGR1134"],"award-info":[{"award-number":["2017SGR1134"]}]},{"name":"the European Union","award":["PI17\/01067"],"award-info":[{"award-number":["PI17\/01067"]}]},{"name":"the European Union","award":["PI18\/0049"],"award-info":[{"award-number":["PI18\/0049"]}]},{"name":"the European Union","award":["PI21\/00935"],"award-info":[{"award-number":["PI21\/00935"]}]},{"name":"the European Union","award":["PI21\/01085"],"award-info":[{"award-number":["PI21\/01085"]}]},{"name":"the European Union","award":["PI20\/0448"],"award-info":[{"award-number":["PI20\/0448"]}]},{"name":"the European Union","award":["2017SGR1134"],"award-info":[{"award-number":["2017SGR1134"]}]},{"name":"AGAUR from the  Autonomous Catalan Government","award":["PI17\/01067"],"award-info":[{"award-number":["PI17\/01067"]}]},{"name":"AGAUR from the  Autonomous Catalan Government","award":["PI18\/0049"],"award-info":[{"award-number":["PI18\/0049"]}]},{"name":"AGAUR from the  Autonomous Catalan Government","award":["PI21\/00935"],"award-info":[{"award-number":["PI21\/00935"]}]},{"name":"AGAUR from the  Autonomous Catalan Government","award":["PI21\/01085"],"award-info":[{"award-number":["PI21\/01085"]}]},{"name":"AGAUR from the  Autonomous Catalan Government","award":["PI20\/0448"],"award-info":[{"award-number":["PI20\/0448"]}]},{"name":"AGAUR from the  Autonomous Catalan Government","award":["2017SGR1134"],"award-info":[{"award-number":["2017SGR1134"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>The objective of this study is to describe the alterations occurring during the neurodegenerative process in skin fibroblast cultures from C9orf72 patients. We characterized the oxidative stress, autophagy flux, small ubiquitin-related protein SUMO2\/3 levels as well as the mitochondrial function in skin fibroblast cultures from C9orf72 patients. All metabolic and bioenergetic findings were further correlated with gene expression data obtained from RNA sequencing analysis. Fibroblasts from C9orf72 patients showed a 30% reduced expression of C9orf72, ~3-fold increased levels of oxidative stress and impaired mitochondrial function obtained by measuring the enzymatic activities of mitochondrial respiratory chain complexes, specifically of complex III activity. Furthermore, the results also reveal that C9orf72 patients showed an accumulation of p62 protein levels, suggesting the alteration of the autophagy process, and significantly higher protein levels of SUMO2\/3 (p = 0.03). Our results provide new data reinforcing that C9orf72 cells suffer from elevated oxidative damage to biomolecules and organelles and from increased protein loads, leading to insufficient autophagy and an increase in SUMOylation processes.<\/jats:p>","DOI":"10.3390\/antiox11061129","type":"journal-article","created":{"date-parts":[[2022,6,9]],"date-time":"2022-06-09T10:49:14Z","timestamp":1654771754000},"page":"1129","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Bioenergetic and Autophagic Characterization of Skin Fibroblasts from C9orf72 Patients"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3788-8915","authenticated-orcid":false,"given":"Maria Isabel","family":"Alvarez-Mora","sequence":"first","affiliation":[{"name":"Biochemistry and Molecular Genetics Department, Hospital Clinic of Barcelona, 08036 Barcelona, Spain"},{"name":"CIBER of Rare Diseases (CIBERER), 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Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4746-1034","authenticated-orcid":false,"given":"Laura","family":"Gort","sequence":"additional","affiliation":[{"name":"Biochemistry and Molecular Genetics Department, Hospital Clinic of Barcelona, 08036 Barcelona, Spain"},{"name":"CIBER of Rare Diseases (CIBERER), Instituto de Salud Carlos III, 08036 Barcelona, Spain"},{"name":"Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergi","family":"Borrego-\u00c9cija","sequence":"additional","affiliation":[{"name":"Alzheimer\u2019s Disease and Other Cognitive Disorders, Neurology Service, Hospital Clinic de Barcelona, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7750-896X","authenticated-orcid":false,"given":"Raquel","family":"Sanchez-Valle","sequence":"additional","affiliation":[{"name":"Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain"},{"name":"Alzheimer\u2019s Disease and Other Cognitive Disorders, Neurology Service, Hospital Clinic de Barcelona, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0272-7014","authenticated-orcid":false,"given":"Judith","family":"Canto-Santos","sequence":"additional","affiliation":[{"name":"CIBER of Rare Diseases (CIBERER), Instituto de Salud Carlos III, 08036 Barcelona, Spain"},{"name":"Muscle Research and Mitochondrial Function Laboratory Cellex-IDIBAPS, Faculty of Medicine and Health Sciences, University of Barcelona, Internal Medicine Department, Hospital Clinic of Barcelona, 08036 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