Investigating Mitochondrial Dysfunction to Increase Drug Safety in the Pharmaceutical Industry

Sashi      Nadanaciva; Yvonne      Will

Abstract

Drug-induced mitochondrial dysfunction is a contributor to both late-stage compound attrition and post-market drug withdrawals. This review outlines the mechanisms which lead to drug-induced mitochondrial dysfunction and discusses the tremendous advances that have been made in the development of in vitro methods to identify mitochondrial impairment. Potentially useful animal models and in vivo methods to detect drug-induced mitochondrial impairment are also discussed.

Keywords: Mitochondrial dysfunction, oxidative phosphorylation, organ toxicity, mitochondrial diseases, drug safety, bioenergetics, mutation, metabolomics, dyslipidemia, NSAID, water, synthesis, organic