Clinical consequences of drug-induced mitochondrial dysfunction

Mitochondria are the main energy producers of the cell, providing energy in the form of adenosine triphosphate. Drug-induced toxicity may directly target mitochondria in various organs including the liver, heart, and kidney, as well as in organ systems such as the auditory, nervous, and muscular, which can result in clinical consequences. Understanding the causes and mechanisms of drug-induced mitochondrial dysfunction (DIMD) can enable the better prediction of mitochondrial toxicity in early stages of drug development. In this chapter, we will introduce the organs and organ systems most commonly affected by mitochondrial intoxication, specifically focussing on drugs and will describe the role of DIMD in the pathogenesis toxicity. We will also consider the influence of interindividual variation on the risk of DIMD and discuss the importance of appropriate and thorough preclinical testing in order to mitigate the risk of drugs carrying unidentified mitochondrial liabilities.