Mechanism of the formation of megamitochondria induced by copper-chelating agents. III. Formation and some biochemical properties of megamitochondria induced by diethyldithiocarbamate (DDC).

Sodium diethyldithiocarbamate (DDC), a copper-chelating agent, has induced megamitochondria in mouse hepatocytes simply by feeding the animal with a diet containing the noxious agent. Megamitochondria have been isolated from the liver, specified above, in a medium containing albumin. Phosphorylating capacities of such megamitochondria have revealed that they are tightly coupled. Biochemical properties of megamitochondria, such as cytochrome contents, activities of copper-containing enzymes. and contents of Cu2+, strongly suggest that copper-chelating action of the agent may not be related to the formation of megamitochondria just as in the case of cuprizone-induced megamitochondria. Moreover, contents of divalent metals such as Ca2+ and Mg2+ were drastically decreased in the mitochondrial preparation specified above. Similarities in biochemical aspects of DDC-induced megamitochondria to those of cuprizone-induced megamitochondria together with ultrastructural changes in the liver and clinical appearances of the mouse treated with the agent would strongly suggest that the mechanism of the formation of megamitochondria induced either by DDC or by cuprizone may be the same.