Biological and Computational Techniques to Identify Mitochondrial Toxicants

Mitochondrial toxicity is a common cause of drug toxicity and failure in clinical trials. To prevent unwanted mitochondrial toxicity in new drugs, high-throughput screening techniques for mitochondrial toxicity must be developed and implemented. In particular, measuring oxygen consumption rate (OCR) allows for the rapid testing of compounds for mitochondrial toxicity and the identification of mechanisms of mitochondrial toxicity. Additionally, in silico techniques such as quantitative structure-activity relationship (QSAR) and toxicophore modeling can identify chemical features that cause mitochondrial toxicity. This chapter summarizes methods for testing mitochondrial toxicity with an emphasis on the advantages and challenges of measuring OCR and provides an overview of the application of QSAR and toxicophore models to mitochondrial toxicity.