Drug-induced Lysosomal, Mitochondrial, and Peroxisomal Disorders

摘要

In the current drug development environment, three organelles routinely undergo scrutiny for detection of drug-induced change: lysosomes due to their ubiquitous distribution and propensity for morphologic change; peroxisomes due to the intense effortsto identify effective drugs to lower cholesterol or with PPARa activity; and, mitochondria due to the adverse consequences occurring secondary to dysfunction. Key to evaluation is a pathology assessment, necessitating a basic understanding of drug-induced changes in these commonly affected organelles. Lysosomes comprise the cellular digestive system and are a major contributor to membrane repair. Peroxisomes prevent injury to the cell from reactive molecules that are by-products of metabolism. Mitochondria are the cell's power supply, providing oxidative respiration for sustained energy supply. These functions dictate the types of morphologic and functional changes that occur secondary to drug administration, and the potential implications of these effects.