Mitochondria-Targeted Cytochromes P450 Modulate Adverse Drug Metabolism and Xenobiotic-Induced Toxicity

This chapter discusses the molecular mechanism(s) of targeting of some of the cytochrome P450s (CYPs) to mitochondria, and assesses their roles in the metabolism of diverse drugs. It then discusses the significance of mitochondrial drug metabolism in mitochondrial toxicity, oxidative stress, and inflammatory-associated tissue injury. The chapter also focuses on highlighting the multimodal targeting mechanisms of CYPs to mitochondria and their role in drug metabolism and toxicity under physiological and patho-physiological conditions. Mitochondria-based drug metabolisms are involved in controlling the physiological processes as well as in a number of toxicities and diseases. Both mitochondrial DNA and metabolic systems are highly sensitive to changes in the intramitochondrial and extramitochondrial environments. Mitochondria-targeted CYPs play a significant role in the generation of reactive oxygen species (ROS). At low levels, mitochondrial ROS are key signaling molecules that connect mitochondrial respiratory chain to communicate with the remainder of the cell to control numerous physiological and pathological responses.