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 r at liver mitochondria has been studied with particular emphasis on its sensitivity to inhibitors of respiration. We found that the Q cycle p layed an important part in cyanide-resistant respiration. The extent t o 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 thro ugh the o-center of the cycle. Under these conditions mixothiazole and antimycin A inhibited the respiration by 70-80 and 20-30%, respective ly. In the presence of either agent cytochrome b was oxidized by menad ione. When rotenone was introduced into the medium, menadione was redu ced by DT diaphorase and the rate of cyanide-resistant respiration dec reased approximately two-fold; mixothiazole and antimycin inhibited th e respiration by 40%. In the absence of rotenone and dicumarol, cyanid e-resistant respiration was insensitive to both inhibitors of the Q cy cle. It is concluded that cyanide-resistant respiration depends on bot h 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 a nd cycle (i.e., sensitivity of the respiration to mixothiazole and ant imycin) is reduced