NQO1 in protection against oxidative stress

Abstract NQO1 can be induced by multiple forms of stress including oxidative stress. NQO1 is a pleiotropic enzyme and consideration of some of the known endogenous substrates and functions of NQO1 may explain the potential beneficial effects of NQO1 against oxidative stress. NQO1 can reduce ubiquinone and vitamin E quinone to antioxidant forms and can reduce superoxide directly which suggests a primary protective role. However, the rate constant for superoxide reduction by NQO1 is low and this reaction is only likely to be relevant where NQO1 levels are high and superoxide dismutase levels are low. NQO1 can participate in protein-protein interactions, protecting other proteins including p53 against 20S proteasomal degradation. This suggests one important role for NQO1 when induced under stress is to maintain the stability of critical proteins such as p53 and other transcription factors. RNA-protein interactome studies have also shown that NQO1 can bind to mRNA and modulate protein levels by affecting translation. Changes in the redox balance of pyridine nucleotides, which occurs during oxidative stress, alters the conformation and resultant binding of NQO1 to macromolecules. Whether this behavior of NQO1 is relevant for protection or signaling during oxidative stress remains to be determined.