Coenzyme Q 1 redox metabolism during passage through the rat pulmonary circulation and the effect of hyperoxia

The objective was to evaluate the pulmonary disposition of the ubiquinone homolog coenzyme Q 1 (CoQ 1 ) on passage through lungs of normoxic (exposed to room air) and hyperoxic (exposed to 85% O 2 for 48 h) rats. CoQ 1 or its hydroquinone (CoQ 1 H 2 ) was infused into the arterial inflow of isolated, perfused lungs, and the venous efflux rates of CoQ 1 H 2 and CoQ 1 were measured. CoQ 1 H 2 appeared in the venous effluent when CoQ 1 was infused, and CoQ 1 appeared when CoQ 1 H 2 was infused. In normoxic lungs, CoQ 1 H 2 efflux rates when CoQ 1 was infused decreased by 58 and 33% in the presence of rotenone (mitochondrial complex I inhibitor) and dicumarol [NAD(P)H-quinone oxidoreductase 1 (NQO1) inhibitor], respectively. Inhibitor studies also revealed that lung CoQ 1 H 2 oxidation was via mitochondrial complex III. In hyperoxic lungs, CoQ 1 H 2 efflux rates when CoQ 1 was infused decreased by 23% compared with normoxic lungs. Based on inhibitor effects and a kinetic model, the effect of hyperoxia could be attributed predominantly to 47% decrease in the capacity of complex I-mediated CoQ 1 reduction, with no change in the other redox processes. Complex I activity in lung homogenates was also lower for hyperoxic than for normoxic lungs. These studies reveal that lung complexes I and III and NQO1 play a dominant role in determining the vascular concentration and redox status of CoQ 1 during passage through the pulmonary circulation, and that exposure to hyperoxia decreases the overall capacity of the lung to reduce CoQ 1 to CoQ 1 H 2 due to a depression in complex I activity.