A yeast-based assay identifies drugs active against human mitochondrial disorders

Elodie Couplan, Raeka S. Aiyar, Roza Kucharczyk, Anna Kabala, Nahia Ezkurdia, Julien Gagneur, Robert P. St. Onge, Bénédicte Salin, Flavie Soubigou, Marie Le Cann, Lars M. Steinmetz, Jean Paul Di Rago, Marc Blondel

Research output: Contribution to journalArticlepeer-review

69 Scopus citations


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.

Original languageEnglish
Pages (from-to)11989-11994
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number29
StatePublished - 19 Jul 2011
Externally publishedYes


  • Budding yeast
  • Drug screening
  • NARP cybrid
  • Transcription profiling


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