抄録
Mitochondria have recently gained renewed interest in toxicology because of their pivotal role in signaling and mediating cell death in certain cell types. This Educational Lecture will present basic concepts of mitochondrial function and review how diverse toxicants can disrupt these functions, activate signaling pathways, cause cumulative damage, and eventually lead to cell death. Of particular importance are the generation of mitochondrial ROS and RNS and imbalances in the mitochondrial antioxidant status, the production of reactive metabolites, the induction of the permeability transition and outer membrane permeabilization, and the unique nature and vulnerability of mitochondrial DNA. The lecture will also present a new concept on the role of mitochondria in idiosyncratic drug-induced liver injury (DILI). Experimental evidence with transgenic mouse models suggests that underlying genetic abnormalities in mitochondria may augment mitochondrial injury induced by certain mitochondria-targeting drugs and unmask the potential for DILI. Finally, a better understanding of the mitochondrial cell death-inducing pathways (including JNK activation) may open new avenues for therapeutic intervention by mechanism-based targeting of these pathways.
