{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T16:47:32Z","timestamp":1781714852683,"version":"3.54.5"},"reference-count":76,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2021,4,24]],"date-time":"2021-04-24T00:00:00Z","timestamp":1619222400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Mitochondrial diseases result from inherited or spontaneous mutations in mitochondrial or nuclear DNA, leading to an impairment of the oxidative phosphorylation responsible for the synthesis of ATP. To date, there are no effective pharmacological therapies for these pathologies. We performed a yeast-based screening to search for therapeutic drugs to be used for treating mitochondrial diseases associated with dominant mutations in the nuclear ANT1 gene, which encodes for the mitochondrial ADP\/ATP carrier. Dominant ANT1 mutations are involved in several degenerative mitochondrial pathologies characterized by the presence of multiple deletions or depletion of mitochondrial DNA in tissues of affected patients. Thanks to the presence in yeast of the AAC2 gene, orthologue of human ANT1, a yeast mutant strain carrying the M114P substitution equivalent to adPEO-associated L98P mutation was created. Five molecules were identified for their ability to suppress the defective respiratory growth phenotype of the haploid aac2M114P. Furthermore, these molecules rescued the mtDNA mutability in the heteroallelic AAC2\/aac2M114P strain, which mimics the human heterozygous condition of adPEO patients. The drugs were effective in reducing mtDNA instability also in the heteroallelic strain carrying the R96H mutation equivalent to the more severe de novo dominant missense mutation R80H, suggesting a general therapeutic effect on diseases associated with dominant ANT1 mutations.<\/jats:p>","DOI":"10.3390\/ijms22094461","type":"journal-article","created":{"date-parts":[[2021,4,24]],"date-time":"2021-04-24T21:49:20Z","timestamp":1619300960000},"page":"4461","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["A Yeast-Based Screening Unravels Potential Therapeutic Molecules for Mitochondrial Diseases Associated with Dominant ANT1 Mutations"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7705-2971","authenticated-orcid":false,"given":"Giulia","family":"di Punzio","sequence":"first","affiliation":[{"name":"Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, Parco Area delle Scienze 11\/A, 43124 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Antonietta","family":"Di Noia","sequence":"additional","affiliation":[{"name":"Laboratory of Biochemistry and Molecular Biology, Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, 70125 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agn\u00e8s","family":"Delahodde","sequence":"additional","affiliation":[{"name":"Institute for Integrative Biology of the Cell (I2BC), Universit\u00e9 Paris-Saclay, 91198 Gif-sur-Yvette, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carole","family":"Sellem","sequence":"additional","affiliation":[{"name":"Institute for Integrative Biology of the Cell (I2BC), Universit\u00e9 Paris-Saclay, 91198 Gif-sur-Yvette, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4901-2358","authenticated-orcid":false,"given":"Claudia","family":"Donnini","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, Parco Area delle Scienze 11\/A, 43124 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6503-2922","authenticated-orcid":false,"given":"Luigi","family":"Palmieri","sequence":"additional","affiliation":[{"name":"Laboratory of Biochemistry and Molecular Biology, Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, 70125 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiziana","family":"Lodi","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, Parco Area delle Scienze 11\/A, 43124 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4397-9143","authenticated-orcid":false,"given":"Cristina","family":"Dallabona","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, Parco Area delle Scienze 11\/A, 43124 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1007\/BF01799603","article-title":"Clinical Aspects of Mitochondrial Disorders","volume":"15","author":"Munnich","year":"1992","journal-title":"J. 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