High-throughput screening of FDA-approved drugs using oxygen biosensor plates reveals secondary mitofunctional effects

Sunil Sahdeo, Alexey Tomilov, Kelly Komachi, Christine Iwahashi, Sandipan Datta, Owen Hughes, Paul J Hagerman, Gino A Cortopassi

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Repurposing of FDA-approved drugs with effects on mitochondrial function might shorten the critical path to mitochondrial disease drug development. We improved a biosensor-based assay of mitochondrial O2 consumption, and identified mitofunctional defects in cell models of LHON and FXTAS. Using this platform, we screened a 1600-compound library of clinically used drugs. The assay identified drugs known to affect mitochondrial function, such as metformin and decoquinate. We also identified several drugs not previously known to affect mitochondrial respiration including acarbose, metaraminol, gallamine triethiodide, and acamprosate. These previously unknown 'mitoactives' represent novel links to targets for mitochondrial regulation and potentially therapy, for mitochondrial disease.

Original languageEnglish (US)
Pages (from-to)116-125
Number of pages10
JournalMitochondrion
Volume17
DOIs
StatePublished - 2014

Keywords

  • Bioenergetics
  • High-throughput screening
  • Mitochondrial disease
  • Oxygen

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Molecular Medicine

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