Datta Sandipan, Sahdeo Sunil, Gray Jennifer A, Morriseau Christophe, Hammock Bruce D, Cortopassi Gino
Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, 1089 Veterinary Medicine Drive, Davis, CA, 95616, USA.
Department of Entomology and Nematology, and UCD Comprehensive Cancer Center, University of California, Davis, One Shields Avenue, Davis, CA 95616, USA.
Mitochondrion. 2016 Nov;31:79-83. doi: 10.1016/j.mito.2016.10.001. Epub 2016 Oct 4.
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.
线粒体毒性正逐渐成为导致严重人类健康后果的主要机制。这项研究利用先前报道的生物传感器平台，对176种环境化学物质进行了线粒体毒性的高通量筛选（HTS）。这项已建立的高通量筛选证实了已知的线粒体毒素，并鉴定出新型线粒体解偶联剂，如2,2'-亚甲基双（4-氯苯酚）和五氯苯酚。从多种环境氯酚是线粒体抑制剂和解偶联剂这一意义上来说，该研究还确定了线粒体的“构效关系”（SAR）。本研究证明了概念验证，即线粒体高通量筛选检测法可检测已知和新型环境线粒体毒性物质，并可用于快速评估环境中线粒体毒性物质对人类健康的风险。
