No abstract

No abstract

No abstract

No abstract

Correlation between the chemical structure and the ability to induce hepatic megamitochondria formation was studied by feeding mice and rats diets containing a wide spectrum of ammonia derivatives.1. Ammonia derivatives with electron-releasing groups, such as hydrazine, phenylhydrazine, hydroxylamine and aniline were effective in inducing megamitochondria.2. Ammonia derivatives with electron-withdrawing groups, such as formamide, sulfamic acid, acetamide were ineffective in inducing megamitochondria.3. Inducibility of ammonia derivatives with electron-releasing groups plus electron-withdrawing groups for the megamitochondria formation was dependent upon nucleophilicity of the chemical : 2,4-dinitrophenylhydrazine induced megamitochondria, while acetanilide did not induce megamitochondria.4. The megamitochondria formation induced by ammonia derivatives was a reversible process. 5.Freeze-fracture studies on megamitochondria indicated that megamitochondria were formed by the fusion of adjacent mitochondria.6. Phosphorylating capacity of megamitochondria (hydrazine-induced megamitochondria, for example) were normal despite morphological changes.These data might suggest that the nucleophilicity of chemicals plays a key role in the induction of hepatic megamitochondria. These data might also suggest that the phenomenon is an adaptive process to changes of intracellular milieu.There is a vast literature describing the megamitochondria formation both in physiological and pathological conditions (for a review, see [l -41). Recent studies on mitochondria1 three-dimensional structures using the serial sectioning technique have revealed that in several tissues and isolated cells there exist two to three huge, branching mitochondria per cell [5, 61. In extreme cases only one branching mitochondrion has been reported to exist per cell [7]. However, the meaning of the existence of megamitochondria in the pathological and physiological conditions is obscure. If the structural changes of mitochondria reflect a change in function, formation of megamitochondria would be an important phenomenon to study.Previously we have shown that the isonicotinic acid derivatives such as nialamide and isoniazid induce megamitochondria in the mouse hepatocytes when animals are fed these agents [S]. The studies on biochemical aspects of megamitochondria induced by these agents have revealed that the monoamine oxidase activity is specifically decreased [8]. These agents also inhibited monoamine oxidase activity in mitochondria isolated from normal animals [8]. Thus, we have postulated that the inhibitory effect of monoamine oxidase is in some way related to the mechanism of megamitochondria formation. However, during the course of the investigation we have found that there are several reagents which inhibit monoamine oxidase activity both in vivo and in vitro and yet megamitochondria were not observed. Thus, we have looked for the structural similarities among the inducers of megamitochondria and have postulated that the chemical inducers of megami...