EFFECT OF Q-CYCLE INHIBITORS ON MENADIONE-INDUCED CYANIDE-RESISTANT MALATE OXIDATION BY RAT-LIVER MITOCHONDRIA

Cyanide-resistant malate oxidation induced by menadione (90 mu M) in rat liver mitochondria has been studied with particular emphasis on its sensitivity to inhibitors of respiration. We found that the Q cycle played an important part in cyanide-resistant respiration. The extent to which electron-transporting components of the cycle were involved in the process under study was determined by the mode of electron supply. In the presence of dicumarol both CoQ and menadione were reduced by NADH-dependent quinone reductase and the bulk of electrons passed through the o-center of the cycle. Under these conditions mixothiazole and antimycin A inhibited the respiration by 70-80 and 20-30%, respectively. In the presence of either agent cytochrome b was oxidized by menadione. When rotenone was introduced into the medium, menadione was reduced by DT diaphorase and the rate of cyanide-resistant respiration decreased approximately two-fold; mixothiazole and antimycin inhibited the respiration by 40%. In the absence of rotenone and dicumarol, cyanide-resistant respiration was insensitive to both inhibitors of the Q cycle. It is concluded that cyanide-resistant respiration depends on both the ratio of reduction rates ofthe two quinones, K-3 and CoQ and the osmolarity of the medium. In hypotonic media the involvement of the and cycle (i.e., sensitivity of the respiration to mixothiazole and antimycin) is reduced