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Oxidative Medicine and Cellular Longevity
Volume 2015, Article ID 565140, 10 pages
Research Article

A Yeast/Drosophila Screen to Identify New Compounds Overcoming Frataxin Deficiency

1“Mitochondries, Métaux et Stress Oxydant”, Institut Jacques Monod, UMR7592 CNRS-Université Paris Diderot, Sorbonne Paris Cité, 15 rue Hélène Brion, 75205 Paris Cedex 13, France
2Unité de Biologie Fonctionnelle et Adaptative (BFA), UMR8251 CNRS-Université Paris Diderot, Sorbonne Paris Cité, 4 rue M. A. Lagroua Weill Halle, 75205 Paris Cedex 13, France
3Laboratoire d’Innovation Thérapeutique, UMR7200 CNRS-Université de Strasbourg, Faculté de Pharmacie, 74 route du Rhin, BP 60024, 67401 Illkirch Cedex, France

Received 24 October 2014; Revised 26 December 2014; Accepted 6 January 2015

Academic Editor: Cláudio M. Gomes

Copyright © 2015 Alexandra Seguin et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Friedreich’s ataxia (FA) is a rare neurodegenerative disease which is very debilitating for the patients who progressively lose their autonomy. The lack of efficient therapeutic treatment of the disease strongly argues for urgent need to search for new active compounds that may stop the progression of the disease or prevent the appearance of the symptoms when the genetic defect is diagnosed early enough. In the present study, we used a yeast strain with a deletion of the frataxin homologue gene as a model of FA cells in a primary screen of two chemical libraries, a fraction of the French National Chemical Library (5500 compounds) and the Prestwick collection (880 compounds). We ran a secondary screen on Drosophila melanogaster flies expressing reduced levels of frataxin during larval development. Half of the compounds selected in yeast appeared to be active in flies in this developmental paradigm, and one of the two compounds with highest activities in this assay partially rescued the heart dilatation phenotype resulting from heart specific depletion of frataxin. The unique complementarity of these two frataxin-deficient models, unicellular and multicellular, appears to be very efficient to select new compounds with improved selectivity, bringing significant perspectives towards improvements in FA therapy.