INDUCTION OF MEGAMITOCHONDRIA IN THE MOUSE-LIVER BY ISONICOTINIC-ACID DERIVATIVES

Megamitochondria were induced in mouse hepatocytes simply by feeding the animal for 7 to 10 days with a diet containing isonicotinic acid derivatives, namely, nialamide, isoniazid, and iproniazid. Monoamine oxidase activities of megamitochondria were invariably decreased significantly. Isonicotinic acid, however, did not induce megamitochondria and had no effect on monoamine oxidase activity of mitochondria. Coupling efficiencies of megamitochondria induced by the reagents, specified above, were not affected. Cytochrome c oxidase and ATPase activities of megamitochondria were also unchanged compared to the control. Isoniazid, iproniazid, and nialamide affected monoamine oxidase activity of mitochondria not only in vivo, as described above, but also in vitro: the activity was inhibited by 50% at concentrations of 5.8 mM, 215 and 140 μM for isoniazid, iproniazid, and nialamide, respectively. Rotenone-insensitive NADH-cytochrome c reductase of megamitochondria, another marker enzyme for mitochondrial outer membrane besides monoamine oxidase, was not affected so much: the lowest activity was 88.6% of the control in the case of nialamide-induced megamitochondria. These reagents had no effect on the enzyme activity in vitro. These data seem to indicate that the reagents examined in the present study affected monoamine oxidase specifically. Mechanism of the formation of megamitochondria is discussed with respect to membrane fusion phenomenon. © 1979.