ABSTRACT
Liver cell death is a prominent feature of drug-induced liver injury (DILI). The major hepatocyte cell death subroutines, apoptosis and necrosis, occur through mitochondrial pathways (MOMP and MPT). DILI is broadly categorized into direct hepatotoxicity and idiosyncratic hepatotoxicity. Mitochondria are central players in liver pathophysiology. In many instances of direct hepatotoxicity, drugs directly cause mitochondrial damage by interfering with mitochondrial homeostatic processes such as respiration, DNA synthesis, or β-oxidation among others. In idiosyncratic DILI, the involvement of mitochondria is more indirect as the cell death mode in this instance is through adaptive immunity (HLA-linked) and largely apoptotic. Since adaptive immunity seems to play a prominent role in idiosyncratic DILI, host factors such as genetics and mitochondrial tness may contribute to the susceptibility for injury. In this chapter, we examine the role of mitochondria in hepatotoxicity both as direct targets of toxins and in idiosyncratic DILI.
