Mitochondrial toxicity of organic arsenicals: membrane permeability transition pore opening and respiratory dysfunction.

In order to clarify the mitochondrial toxicity mechanism of the organic arsenical (2-methoxy-4-(((4-(oxoarsanyl) phenyl) imino) methyl) phenol), research was carried out at the sub-cell level based on the previous finding that the compound can damage the mitochondria by triggering a burst of ROS. After investigating its influence on isolated mitochondria , it was demonstrated that a high dose of with short-term exposure can induce mitochondrial swelling, decrease the membrane potential, enhance the permeability of H and K, and induce membrane lipid peroxidation, indicating that it can result in an MPT process in a ROS-mediated and Ca-independent manner. Additionally, MPT was also aggravated as a result of impairment of the membrane integrity and membrane fluidity. In addition, short-term incubation between mitochondria and compound promoted the inhibition of respiratory chain complexes I, II, III and IV, as well as damage to the respiration process, which supported the previous finding about the burst of ROS. On the other hand, after long-term exposure by the organic arsenical , mitochondrial metabolic dysfunction was triggered, which was in accordance with perturbation of the respiratory chain complexes as well as the respiration process. This work systematically sheds light on the mitochondrial toxicity mechanism of the organic arsenical , including induction of the MPT process and inhibition of respiratory metabolism, which provides a potential target for organic arsenicals as anti-tumor drugs.