Abstract: Cellular ubiquinone (UQ) is expected to act as an endogenous antioxidant against oxidative stress. To confirm this, UQ‐reductases which are necessary to regenerate ubiquinol (UQH_{2}) were investigated in rat tissue, and a novel NADPH‐dependent UQ (NADPH‐UQ) reductase was found in cytosol. The cytosolic NADPH‐UQ reductase activity accounted for more than 80% of UQ‐10 reduction by the rat liver homogenate in the presence of NADPH. Furthermore, the NADPH‐UQ reductase activities in various tissues were correlated to the redox states of UQ in the corresponding tissues. Rat liver cytosol with NADPH protected lecithin liposomes containing UQ‐10, as well as UQH_{2}‐10 from AMVN (2,2'‐azobis(2,4‐dimethyl‐valeronitrile))‐induced lipid peroxidation. The enzyme purified from rat liver cytosol, reduced UQ‐10 in lecithin liposomes at approximately the same rate as did cytosol. These results supported that cytosolic NADPH‐UQ reductase is the enzyme responsible for nonmitochondrial UQ reduction acting as an endogenous antioxidant against oxidative stress. The antioxidant role of the UQ redox cycle and NADPH‐UQ reductase was discussed in relation to other cellular NADPH‐dependent antioxidant enzymes.
