{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T20:12:31Z","timestamp":1791231151366,"version":"4.1.0"},"reference-count":60,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2024,3,18]],"date-time":"2024-03-18T00:00:00Z","timestamp":1710720000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fondazione Italiana per la Ricerca sul Cancro, AIRC","award":["20316"],"award-info":[{"award-number":["20316"]}]},{"name":"Fondazione Italiana per la Ricerca sul Cancro, AIRC","award":["2017 89LFKB"],"award-info":[{"award-number":["2017 89LFKB"]}]},{"name":"Ministero dell\u2019Universit\u00e0 e della Ricerca","award":["20316"],"award-info":[{"award-number":["20316"]}]},{"name":"Ministero dell\u2019Universit\u00e0 e della Ricerca","award":["2017 89LFKB"],"award-info":[{"award-number":["2017 89LFKB"]}]},{"name":"Italian Association for Fragile X syndrome","award":["20316"],"award-info":[{"award-number":["20316"]}]},{"name":"Italian Association for Fragile X syndrome","award":["2017 89LFKB"],"award-info":[{"award-number":["2017 89LFKB"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Mitochondria are involved in multiple aspects of neurodevelopmental processes and play a major role in the pathogenetic mechanisms leading to neuro-degenerative diseases. Fragile-X-related disorders (FXDs) are genetic conditions that occur due to the dynamic expansion of CGG repeats of the FMR1 gene encoding for the RNA-binding protein FMRP, particularly expressed in the brain. This gene expansion can lead to premutation (PM, 56\u2013200 CGGs), full mutation (FM, &gt;200 CGGs), or unmethylated FM (UFM), resulting in neurodegeneration, neurodevelopmental disorders, or no apparent intellectual disability, respectively. To investigate the mitochondrial mechanisms that are involved in the FXD patients, we analyzed mitochondrial morphology and bioenergetics in fibroblasts derived from patients. Donut-shaped mitochondrial morphology and excessive synthesis of critical mitochondrial proteins were detected in FM, PM, and UFM cells. Analysis of mitochondrial oxidative phosphorylation in situ reveals lower respiration in PM fibroblasts. Importantly, mitochondrial permeability transition-dependent apoptosis is sensitized to reactive oxygen species in FM, PM, and UFM models. This study elucidated the mitochondrial mechanisms that are involved in the FXD phenotypes, and indicated altered mitochondrial function and morphology. Importantly, a sensitization to permeability transition and apoptosis was revealed in FXD cells. Overall, our data suggest that mitochondria are novel drug targets to relieve the FXD symptoms.<\/jats:p>","DOI":"10.3390\/ijms25063421","type":"journal-article","created":{"date-parts":[[2024,3,18]],"date-time":"2024-03-18T08:17:29Z","timestamp":1710749849000},"page":"3421","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Mitochondrial Dysfunction Causes Cell Death in Patients Affected by Fragile-X-Associated Disorders"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5203-3416","authenticated-orcid":false,"given":"Martina","family":"Grandi","sequence":"first","affiliation":[{"name":"Department of Biomedical and Neuromotor Sciences, University of Bologna, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Galber","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Neuromotor Sciences, University of Bologna, 40126 Bologna, Italy"},{"name":"Institute of Neuroscience, Consiglio Nazionale delle Ricerche, 35121 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1658-8470","authenticated-orcid":false,"given":"Cristina","family":"Gatto","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Neuromotor Sciences, University of Bologna, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronica","family":"Nobile","sequence":"additional","affiliation":[{"name":"Department of Life Sciences and Public Health, Catholic University of Sacred Heart, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecilia","family":"Pucci","sequence":"additional","affiliation":[{"name":"Department of Life Sciences and Public Health, Catholic University of Sacred Heart, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-7981-3675","authenticated-orcid":false,"given":"Ida","family":"Schaldemose Nielsen","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Neuromotor Sciences, University of Bologna, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0234-2587","authenticated-orcid":false,"given":"Francesco","family":"Boldrin","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Padova, 35121 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Neri","sequence":"additional","affiliation":[{"name":"Department of Life Sciences and Public Health, Catholic University of Sacred Heart, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5104-1521","authenticated-orcid":false,"given":"Pietro","family":"Chiurazzi","sequence":"additional","affiliation":[{"name":"Department of Life Sciences and Public Health, Catholic University of Sacred Heart, 00168 Rome, Italy"},{"name":"UOC Medical Genetics, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7825-0446","authenticated-orcid":false,"given":"Giancarlo","family":"Solaini","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Neuromotor Sciences, University of Bologna, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0490-1776","authenticated-orcid":false,"given":"Alessandra","family":"Baracca","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Neuromotor Sciences, University of Bologna, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4229-3054","authenticated-orcid":false,"given":"Valentina","family":"Giorgio","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Neuromotor Sciences, University of Bologna, 40126 Bologna, Italy"},{"name":"Institute of Neuroscience, Consiglio Nazionale delle Ricerche, 35121 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4707-2242","authenticated-orcid":false,"given":"Elisabetta","family":"Tabolacci","sequence":"additional","affiliation":[{"name":"Department of Life Sciences and Public Health, Catholic University of Sacred Heart, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4314","DOI":"10.1172\/JCI63141","article-title":"Fragile X Syndrome: Causes, Diagnosis, Mechanisms, and Therapeutics","volume":"122","author":"Bagni","year":"2012","journal-title":"J. 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