MECHANISM OF THE FORMATION OF MEGAMITOCHONDRIA INDUCED BY COPPER‐CHELATING AGENTS

Megamitochondria have been isolated from the liver of the cuprizone‐fed mouse with the aid of bovine serum albumin. Phosphorylating capacities of megamitochondria, specified above, in terms of respiratory control ratios and ADP/O ratios have revealed that they are not uncoupled completely. Biochemical properties of megamito‐chondria which are related to the metabolism of copper have shown that copper‐chelating action of cuprizone may not be directly related to the formation of megamitochondria in vivo . Namely, cytochrome contents, activities of cytochrome oxidase and monoamine oxidase and contents of copper of megamitochondria were unchanged compared with those of the control. However, contents of divalent metals such as Ca ++ and Mg ++ , especially that of the former, in megamitochondria decreased significantly. It is suggested that cuprizone may alter Mg++/Ca++ ratios when it is administered in vivo , and that changes in the ratio might play a key role in the formation of megamitochondria.