Searching for alternative toxicology testing systems: The response of isolated mitochondria from Saccharomyces cerevisiae, potato tuber, and mouse liver to a toxic insult

Mitochondria are cellular power plants known as essential organelles for energy (ATP) metabolism. However, today it is evident that various vital compounds are partially or exclusively synthesized in mitochondria. Moreover, this organelle plays a pivotal role in essential processes such as cell death. The isolated mitochondrion is an excellent experimental model for evaluating the role of mitochondria in the pathogenesis of diseases. Various in vitro and in vivo experimental models have been developed to study mitochondria. On the other hand, some alternative models could also help decrease the use of animal models. In the current study, we compared the response of mitochondria isolated from mouse liver, saccharomyces cerevisiae (S.c), and potato tuber to various concentrations of calcium (Ca۲+) as a robust mitochondrial disturbing agent. The current study found that significant mitochondrial depolarization, decreased ATP levels, mitochondrial permeabilization, and decreased mitochondrial dehydrogenases activity were found in all isolated mitochondrial preparations. No significant difference between mouse liver, S.c, and potato tuber mitochondria were detected in experiments carried out in the current investigation. We are aware that mitochondria from different species have a huge structural and enzymatic variance. Hence, these models could just estimate the effect of xenobiotics in biological systems. However, the data derived from this study could finally help to decrease the use of experimental animals and provide new approaches for evaluating mitochondrial function.

Keywords:

Alternative toxicology models , ATP , Drug development , Mitochondrial disease , Mitochondrial impairment