On the mechanism of cuprizone-induced formation of megamitochondria in mouse liver

The livers of mice maintained on a diet containing 1% cuprizone for periods up to 18 days formed giant (mega) mitochondria equaling of exceeding the size of the nucleus. The megamitochondria were isolated from the liver and shown to be competent in respect to oxidative phosphorylation, although the P/O ratio and respiratory control index were somewhat reduced. When cuprizone was deleted from the diet, the size and function of the liver mitochondria returned to normal. Electron microscopic studies have made it possible to demonstrate the intermediate steps by which the membranes of paired mitochondria fuse and defuse to form megamitochondria, and from these studies a general mechanism may now be proposed for processes in which one continuous membrane splits into two separate membranes or by which two separated membranes fuse to form one continuous membrane.