title: A high-throughput screen for mitochondrial function reveals known and novel mitochondrial toxicants in a library of environmental agents.
abstract: Mitochondrial toxicity is emerging as a major mechanism underlying serious human health consequences. This work performs a high-throughput screen (HTS) of 176 environmental chemicals for mitochondrial toxicity utilizing a previously reported biosensor platform. This established HTS confirmed known mitochondrial toxins and identified novel mitotochondrial uncouplers such as 2, 2'-Methylenebis(4-chlorophenol) and pentachlorophenol. It also identified a mitochondrial 'structure activity relationship' (SAR) in the sense that multiple environmental chlorophenols are mitochondrial inhibitors and uncouplers. This study demonstrates proof-of-concept that a mitochondrial HTS assay detects known and novel environmental mitotoxicants, and could be used to quickly evaluate human health risks from mitotoxicants in the environment.
authors.affiliation: Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, 1089 Veterinary Medicine Drive, Davis, CA, 95616, USA.
authors.forename: Sandipan
authors.initials: S
authors.lastname: Datta
authors.affiliation: Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, 1089 Veterinary Medicine Drive, Davis, CA, 95616, USA.
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, USA.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Gray
authors.affiliation: Department of Entomology and Nematology, and UCD Comprehensive Cancer Center, University of California, Davis, One Shields Avenue, Davis, CA 95616, USA.
authors.forename: Christophe
authors.initials: C
authors.lastname: Morriseau
authors.affiliation: Department of Entomology and Nematology, and UCD Comprehensive Cancer Center, University of California, Davis, One Shields Avenue, Davis, CA 95616, USA.
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Hammock
authors.affiliation: Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, 1089 Veterinary Medicine Drive, Davis, CA, 95616, USA. Electronic address: gcortopassi@ucdavis.edu.
authors.forename: Gino
authors.initials: G
authors.lastname: Cortopassi
mesh_terms: D015374:Biosensing Techniques / Q000379:methods*; D002460:Cell Line; D004734:Energy Metabolism / Q000187:drug effects; D004785:Environmental Pollutants / Q000633:toxicity*; D004847:Epithelial Cells / Q000187:drug effects / Q000502:physiology; D057166:High-Throughput Screening Assays / Q000379:methods*; D006801:Humans; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D014116:Toxicology / Q000379:methods*; D014475:Uncoupling Agents / Q000633:toxicity
chemical_list: D004785:Environmental Pollutants; D014475:Uncoupling Agents
keywords: Bioenergetics; Biosensor; Cell-based assay; Environmental chemicals; High-throughput screening; Mitochondria; Oxygen; Toxicants