4.5 Article

A high-throughput screen for mitochondrial function reveals known and novel mitochondrial toxicants in a library of environmental agents

Journal

MITOCHONDRION
Volume 31, Issue -, Pages 79-83

Publisher

ELSEVIER SCI LTD
DOI: 10.1016/j.mito.2016.10.001

Keywords

Environmental chemicals; Toxicants; Mitochondria; Oxygen; Bioenergetics; Biosensor; High-throughput screening; Cell-based assay

Funding

  1. NIH awards [RO1 NS077777, RO1 EY012245, PO1 AG025532]

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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. (C) 2016 Elsevier B.V. and Mitochondria Research Society. All rights reserved.

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