Induction of megamitochondria by cuprizone(biscyclohexanone oxaldihydrazone). Evidence for an inhibition of the mitochondrial division process.

1. Feeding weanling mice a diet containing 0.5% (w/w) cuprizone (biscyclohexanone oxaldihydrazone) induced megamitochondria of a different type of that previously described (Suzuki, K., Science 163, 81-82 (1969). 2. As in the normal controls, a single population of mitochondria with a narrow size distribution, was detected by analytical differential centrifugation of liver homogenates from mice fed a cuprizone-diet. However, their average S-value increased 2.4fold, i.e. from 11 500 S to 27 500 S. The marked increase in the mitochondrial size (megamitochondria) were also detected by morphometric analysis of hepatocytes and isolated mitochondrial fractions, and the 1.6fold increase in the average mitochondrial diameter (as determined by scanning electron microscopy) was as expected from the increase in the S-value. On the other hand, the relative volume density or volume fraction of the mitochondria was unchanged. 3. The megamitochondria revealed a normal content of respiratory chain pigments, normal specific respiratory rates with succinate and NADH-linked substrates as well as normal energy coupling. 4. Removal of cuprizone from the diet normalized the size distribution of mitochondria in hepatocytes. The transition followed first-order kinetics with a half-life of about 30 h. During the period dividing mitochondria were frequently observed, and the division process appeared to follow both a transverse-partition and an elongation-constriction mechanism.