{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T18:10:35Z","timestamp":1791223835090,"version":"4.1.0"},"reference-count":45,"publisher":"National Academy of Sciences","issue":"29","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2011,7,19]]},"abstract":"<jats:p>Due to the lack of relevant animal models, development of effective treatments for human mitochondrial diseases has been limited. Here we establish a rapid, yeast-based assay to screen for drugs active against human inherited mitochondrial diseases affecting ATP synthase, in particular NARP (neuropathy, ataxia, and retinitis pigmentosa) syndrome. This method is based on the conservation of mitochondrial function from yeast to human, on the unique ability of yeast to survive without production of ATP by oxidative phosphorylation, and on the amenability of the yeast mitochondrial genome to site-directed mutagenesis. Our method identifies chlorhexidine by screening a chemical library and oleate through a candidate approach. We show that these molecules rescue a number of phenotypes resulting from mutations affecting ATP synthase in yeast. These compounds are also active on human cybrid cells derived from NARP patients. These results validate our method as an effective high-throughput screening approach to identify drugs active in the treatment of human ATP synthase disorders and suggest that this type of method could be applied to other mitochondrial diseases.<\/jats:p>","DOI":"10.1073\/pnas.1101478108","type":"journal-article","created":{"date-parts":[[2011,6,29]],"date-time":"2011-06-29T23:34:04Z","timestamp":1309390444000},"page":"11989-11994","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":95,"title":["A yeast-based assay identifies drugs active against human mitochondrial disorders"],"prefix":"10.1073","volume":"108","author":[{"given":"Elodie","family":"Couplan","sequence":"first","affiliation":[{"name":"INSERM U613; Universit\u00e9 de Brest, Facult\u00e9 de M\u00e9decine et des Sciences de la Sant\u00e9; Etablissement Fran\u00e7ais du Sang (EFS) Bretagne; Centre Hospitalier R\u00e9gional Universitaire Brest, Hop Morvan, Laboratoire de G\u00e9n\u00e9tique Mol\u00e9culaire, F-29200 Brest, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raeka S.","family":"Aiyar","sequence":"additional","affiliation":[{"name":"Genome Biology Unit, European Molecular Biology Laboratory, 69117 Heidelberg, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roza","family":"Kucharczyk","sequence":"additional","affiliation":[{"name":"Institut de Biochimie et de G\u00e9n\u00e9tique Cellulaire, Centre National de la Recherche Scientifique, Universit\u00e9 Victor Segalen Bordeaux 2, Bordeaux, F-33077 Cedex, France;"},{"name":"Institute of Biochemistry and Biophysics, Polish Academy of Sciences, 02-901, Warsaw, Poland; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Kabala","sequence":"additional","affiliation":[{"name":"Institut de Biochimie et de G\u00e9n\u00e9tique Cellulaire, Centre National de la Recherche Scientifique, Universit\u00e9 Victor Segalen Bordeaux 2, Bordeaux, F-33077 Cedex, France;"},{"name":"Institute of Biochemistry and Biophysics, Polish Academy of Sciences, 02-901, Warsaw, Poland; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nahia","family":"Ezkurdia","sequence":"additional","affiliation":[{"name":"Institut de Biochimie et de G\u00e9n\u00e9tique Cellulaire, Centre National de la Recherche Scientifique, Universit\u00e9 Victor Segalen Bordeaux 2, Bordeaux, F-33077 Cedex, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julien","family":"Gagneur","sequence":"additional","affiliation":[{"name":"Genome Biology Unit, European Molecular Biology Laboratory, 69117 Heidelberg, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert P.","family":"St. Onge","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Stanford Genome Technology Center, Stanford University, Palo Alto, CA 94304"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B\u00e9n\u00e9dicte","family":"Salin","sequence":"additional","affiliation":[{"name":"Institut de Biochimie et de G\u00e9n\u00e9tique Cellulaire, Centre National de la Recherche Scientifique, Universit\u00e9 Victor Segalen Bordeaux 2, Bordeaux, F-33077 Cedex, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flavie","family":"Soubigou","sequence":"additional","affiliation":[{"name":"INSERM U613; Universit\u00e9 de Brest, Facult\u00e9 de M\u00e9decine et des Sciences de la Sant\u00e9; Etablissement Fran\u00e7ais du Sang (EFS) Bretagne; Centre Hospitalier R\u00e9gional Universitaire Brest, Hop Morvan, Laboratoire de G\u00e9n\u00e9tique Mol\u00e9culaire, F-29200 Brest, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Le Cann","sequence":"additional","affiliation":[{"name":"INSERM U613; Universit\u00e9 de Brest, Facult\u00e9 de M\u00e9decine et des Sciences de la Sant\u00e9; Etablissement Fran\u00e7ais du Sang (EFS) Bretagne; Centre Hospitalier R\u00e9gional Universitaire Brest, Hop Morvan, Laboratoire de G\u00e9n\u00e9tique Mol\u00e9culaire, F-29200 Brest, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars M.","family":"Steinmetz","sequence":"additional","affiliation":[{"name":"Genome Biology Unit, European Molecular Biology Laboratory, 69117 Heidelberg, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Paul","family":"di Rago","sequence":"additional","affiliation":[{"name":"Institut de Biochimie et de G\u00e9n\u00e9tique Cellulaire, Centre National de la Recherche Scientifique, Universit\u00e9 Victor Segalen Bordeaux 2, Bordeaux, F-33077 Cedex, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Blondel","sequence":"additional","affiliation":[{"name":"INSERM U613; Universit\u00e9 de Brest, Facult\u00e9 de M\u00e9decine et des Sciences de la Sant\u00e9; Etablissement Fran\u00e7ais du Sang (EFS) Bretagne; Centre Hospitalier R\u00e9gional Universitaire Brest, Hop Morvan, Laboratoire de G\u00e9n\u00e9tique Mol\u00e9culaire, F-29200 Brest, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2011,6,29]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2008.06.012"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbabio.2006.04.006"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbabio.2009.09.005"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj3020171"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj20021594"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0509501103"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0091-679X(01)65022-2"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbabio.2009.12.022"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2009.02.011"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddp226"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M703053200"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2003.012047"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.246"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M009557200"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/mus.20598"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddh103"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(94)80310-2"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbabio.2007.05.005"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.22055"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0003-9861(02)00419-8"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M009607200"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M501831200"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt855"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymeth.2006.04.005"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M410789200"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/0005-2728(86)90112-X"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0601091103"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/75556"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-7-113"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.102687599"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.12.2.297"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M309301200"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.14.9386"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi020420w"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7600358"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.07-8581com"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0005-2728(99)00043-2"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/19.8.1777"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0773.1975.tb00766.x"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.4161\/pri.1.1.4053"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0002174"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1002\/biot.200800134"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1002\/biot.200500053"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/0076-6879(79)55021-6"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2007.01.019"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.1101478108","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T19:56:07Z","timestamp":1649793367000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.1101478108"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,6,29]]},"references-count":45,"journal-issue":{"issue":"29","published-print":{"date-parts":[[2011,7,19]]}},"alternative-id":["10.1073\/pnas.1101478108"],"URL":"https:\/\/doi.org\/10.1073\/pnas.1101478108","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,6,29]]},"assertion":[{"value":"2011-06-29","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}