{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,19]],"date-time":"2026-04-19T19:26:41Z","timestamp":1776626801923,"version":"3.51.2"},"reference-count":29,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2020,12,9]],"date-time":"2020-12-09T00:00:00Z","timestamp":1607472000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003407","name":"Ministero dell\u2019Istruzione, dell\u2019Universit\u00e0 e della Ricerca","doi-asserted-by":"publisher","award":["PhD Fellowship"],"award-info":[{"award-number":["PhD Fellowship"]}],"id":[{"id":"10.13039\/501100003407","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Cure RTD Foundation","award":["Grant to Bambino Ges\u00f9 Pediatric Hospital"],"award-info":[{"award-number":["Grant to Bambino Ges\u00f9 Pediatric Hospital"]}]},{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["Cinque per mille and Ricerca Corrente"],"award-info":[{"award-number":["Cinque per mille and Ricerca Corrente"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Riboflavin transporter deficiency (RTD) is a childhood-onset neurodegenerative disorder characterized by sensorineural deafness and motor neuron degeneration. Since riboflavin plays key functions in biological oxidation-reduction reactions, energy metabolism pathways involving flavoproteins are affected in RTD. We recently generated induced pluripotent stem cell (iPSC) lines from affected individuals as an in vitro model of the disease and documented mitochondrial impairment in these cells, dramatically impacting cell redox status. This work extends our study to motor neurons (MNs), i.e., the cell type most affected in patients with RTD. Altered intracellular distribution of mitochondria was detected by confocal microscopic analysis (following immunofluorescence for superoxide dismutase 2 (SOD2), as a dual mitochondrial and antioxidant marker), and \u03b2III-Tubulin, as a neuronal marker. We demonstrate significantly lower SOD2 levels in RTD MNs, as compared to their healthy counterparts. Mitochondrial ultrastructural abnormalities were also assessed by focused ion beam\/scanning electron microscopy. Moreover, we investigated the effects of combination treatment using riboflavin and N-acetylcysteine, which is a widely employed antioxidant. Overall, our findings further support the potential of patient-specific RTD models and provide evidence of mitochondrial alterations in RTD-related iPSC-derived MNs\u2014emphasizing oxidative stress involvement in this rare disease. We also provide new clues for possible therapeutic strategies aimed at correcting mitochondrial defects, based on the use of antioxidants.<\/jats:p>","DOI":"10.3390\/antiox9121252","type":"journal-article","created":{"date-parts":[[2020,12,9]],"date-time":"2020-12-09T09:17:58Z","timestamp":1607505478000},"page":"1252","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Mitochondrial Abnormalities in Induced Pluripotent Stem Cells-Derived Motor Neurons from Patients with Riboflavin Transporter Deficiency"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4894-5084","authenticated-orcid":false,"given":"Fiorella","family":"Colasuonno","sequence":"first","affiliation":[{"name":"Department of Science, LIME, University of Roma Tre, 00146 Rome, Italy"},{"name":"Genetics and Rare Diseases Research Division, IRCCS Ospedale Pediatrico Bambino Ges\u00f9, 00146 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9276-4590","authenticated-orcid":false,"given":"Enrico","family":"Bertini","sequence":"additional","affiliation":[{"name":"Unit of Neuromuscular and Neurodegenerative Diseases, Laboratory of Molecular Medicine, Department of Neuroscience, IRCCS Ospedale Pediatrico Bambino Ges\u00f9, 00146 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marco","family":"Tartaglia","sequence":"additional","affiliation":[{"name":"Genetics and Rare Diseases Research Division, IRCCS Ospedale Pediatrico Bambino Ges\u00f9, 00146 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0877-6172","authenticated-orcid":false,"given":"Claudia","family":"Compagnucci","sequence":"additional","affiliation":[{"name":"Genetics and Rare Diseases Research Division, IRCCS Ospedale Pediatrico Bambino Ges\u00f9, 00146 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1079-3222","authenticated-orcid":false,"given":"Sandra","family":"Moreno","sequence":"additional","affiliation":[{"name":"Department of Science, LIME, University of Roma Tre, 00146 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1002\/jimd.12053","article-title":"An update on the genetics, clinical presentation, and pathomechanisms of human riboflavin transporter deficiency","volume":"42","author":"Bosch","year":"2019","journal-title":"J. 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