Challenges in mitochondrial profiling during pre-clinical studies

Mitochondrial toxicology is a growing field of study focusing disturbances in the natural function of mitochondria, which occur as off-target effects of drugs or other agents. This is an important reason for failure of drugs in clinical trials, which is associated with significant losses of time and money. Failure to detect mitochondrial effects in pre-clinical studies can be explained by limitations in the traditional methodologies, from cell culture to microscopy or bioinformatic analyses. Some of the most popular in vitro models lack physiological relevance, as the widely used culture cell conditions favor pro-glycolytic metabolism and reduce cellular reliance on mitochondria for energy production, which can artificially lower the cells’ sensitivity to mitochondrial toxicants. Several points are also often overlooked in animal models that may lead to inadequate translation of pre-clinical trials into humans. This chapter tackles the most common problems in this area while suggesting some alternatives to overcome them. https://doi.org/10.1016/B978-0-323-88462-4.00002-X