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Mol. Life Sci."],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Friedreich ataxia (FA) is a rare, recessive neuro-cardiodegenerative disease caused by deficiency of the mitochondrial protein frataxin. Mitochondrial dysfunction, a reduction in the activity of iron-sulfur enzymes, iron accumulation, and increased oxidative stress have been described. Dorsal root ganglion (DRG) sensory neurons are among the cellular types most affected in the early stages of this disease. However, its effect on mitochondrial function remains to be elucidated. In the present study, we found that in primary cultures of DRG neurons as well as in DRGs from the FXN\n                    <jats:sup>I151F<\/jats:sup>\n                    mouse model, frataxin deficiency resulted in lower activity and levels of the electron transport complexes, mainly complexes I and II. In addition, altered mitochondrial morphology, indicative of degeneration was observed in DRGs from FXN\n                    <jats:sup>I151F<\/jats:sup>\n                    mice. Moreover, the NAD\n                    <jats:sup>+<\/jats:sup>\n                    \/NADH ratio was reduced and sirtuin activity was impaired. We identified alpha tubulin as the major acetylated protein from DRG homogenates whose levels were increased in FXN\n                    <jats:sup>I151F<\/jats:sup>\n                    mice compared to WT mice. In the mitochondria, superoxide dismutase (SOD2), a SirT3 substrate, displayed increased acetylation in frataxin-deficient DRG neurons. Since SOD2 acetylation inactivates the enzyme, and higher levels of mitochondrial superoxide anion were detected, oxidative stress markers were analyzed. Elevated levels of hydroxynonenal bound to proteins and mitochondrial Fe\n                    <jats:sup>2+<\/jats:sup>\n                    accumulation was detected when frataxin decreased. Honokiol, a SirT3 activator, restores mitochondrial respiration, decreases SOD2 acetylation and reduces mitochondrial superoxide levels. Altogether, these results provide data at the molecular level of the consequences of electron transport chain dysfunction, which starts negative feedback, contributing to neuron lethality. This is especially important in sensory neurons which have greater susceptibility to frataxin deficiency compared to other tissues.\n                  <\/jats:p>","DOI":"10.1007\/s00018-023-05064-4","type":"journal-article","created":{"date-parts":[[2023,12,21]],"date-time":"2023-12-21T14:02:32Z","timestamp":1703167352000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Mitochondrial impairment, decreased sirtuin activity and protein acetylation in dorsal root ganglia in Friedreich Ataxia models"],"prefix":"10.1007","volume":"81","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4614-0581","authenticated-orcid":false,"given":"Arabela","family":"Sanz-Alc\u00e1zar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5069-5574","authenticated-orcid":false,"given":"Elena","family":"Britti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7815-5537","authenticated-orcid":false,"given":"Fabien","family":"Delaspre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8151-1982","authenticated-orcid":false,"given":"Marta","family":"Medina-Carbonero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1267-2491","authenticated-orcid":false,"given":"Maria","family":"Pazos-Gil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3227-6928","authenticated-orcid":false,"given":"Jordi","family":"Tamarit","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0901-8648","authenticated-orcid":false,"given":"Joaquim","family":"Ros","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2795-7999","authenticated-orcid":false,"given":"Elisa","family":"Cabiscol","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,12,21]]},"reference":[{"key":"5064_CR1","doi-asserted-by":"publisher","first-page":"1423","DOI":"10.1126\/SCIENCE.271.5254.1423","volume":"271","author":"V Campuzano","year":"1996","unstructured":"Campuzano V, Montermini L, Molt\u00f2 MD et al (1996) Friedreich\u2019s ataxia: autosomal recessive disease caused by an intronic GAA triplet repeat expansion. 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This work was supported by: 1) Project PID2020-118296RB-I00 funded by MICIU\/AEI \/10.13039\/501100011033; 2) Project CPP2021-008554 funded by MICIU\/AEI \/10.13039\/501100011033 and by the European Union NextGenerationEU\/ PRTR; 3) Project PDC2021-120758-I00 funded by MICIU\/AEI \/10.13039\/501100011033 and by the European Union NextGenerationEU\/ PRTR; 4) Project 2021-SGR 00323 funded by Generalitat de Catalunya. ASA received a Ph.D. fellowship from the Generalitat de Catalunya. Maria Pazos received a PhD fellowship from the Universitat de Lleida.","order":8,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 November 2025","order":9,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Correction","order":10,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"A Correction to this paper has been published:","order":11,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"https:\/\/doi.org\/10.1007\/s00018-025-05948-7","URL":"https:\/\/doi.org\/10.1007\/s00018-025-05948-7","order":12,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors have no relevant financial or non-financial interests to disclose.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"Animal use and care protocol conforms to the National Guidelines for the regulation of the use of experimental laboratory animals from the Generalitat de Catalunya and the Government of Spain (article 33.a 214\/1997) and was evaluated and approved by the Experimental Animal Ethical Committee of the University of Lleida (CEEA).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}}],"article-number":"12"}}