title: High-throughput screening of FDA-approved drugs using oxygen biosensor plates reveals secondary mitofunctional effects.
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.
authors.affiliation: Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, 1089 Veterinary Medicine Drive, Davis, CA 95616, United States.
authors.forename: Sunil
authors.initials: S
authors.lastname: Sahdeo
authors.affiliation: Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, 1089 Veterinary Medicine Drive, Davis, CA 95616, United States.
authors.forename: Alexey
authors.initials: A
authors.lastname: Tomilov
authors.affiliation: Eon Research, 707 4th Street, Suite 305, Davis, CA 95616, United States.
authors.forename: Kelly
authors.initials: K
authors.lastname: Komachi
authors.affiliation: Department of Biochemistry and Molecular Medicine, School of Medicine, University of California, Davis, 4455 Tupper Hall, Davis, CA 95616, United States.
authors.forename: Christine
authors.initials: C
authors.lastname: Iwahashi
authors.affiliation: Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, 1089 Veterinary Medicine Drive, Davis, CA 95616, United States.
authors.forename: Sandipan
authors.initials: S
authors.lastname: Datta
authors.affiliation: Eon Research, 707 4th Street, Suite 305, Davis, CA 95616, United States.
authors.forename: Owen
authors.initials: O
authors.lastname: Hughes
authors.affiliation: Department of Biochemistry and Molecular Medicine, School of Medicine, University of California, Davis, 4455 Tupper Hall, Davis, CA 95616, United States.
authors.forename: Paul
authors.initials: P
authors.lastname: Hagerman
authors.affiliation: Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, 1089 Veterinary Medicine Drive, Davis, CA 95616, United States.
authors.forename: Gino
authors.initials: G
authors.lastname: Cortopassi
mesh_terms: D015374:Biosensing Techniques; D019069:Cell Respiration / Q000187:drug effects*; D055808:Drug Discovery / Q000379:methods*; D057166:High-Throughput Screening Assays / Q000379:methods; D006801:Humans; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D010100:Oxygen / Q000032:analysis*
chemical_list: D010100:Oxygen
keywords: Bioenergetics; High-throughput screening; Mitochondrial disease; Oxygen