Quinone reductases multitasking in the metabolic world

The multiple functions of NAD(P)H:quinone oxidoreductase 1 (NQO1, DT-diaphorase) in the cell are reviewed. NQO1 has long been viewed as a chemoprotective enzyme involved in cellular defense against the electrophilic and oxidizing metabolites of xenobiotic quinones. It also participates in reduction of endogenous quinones, such as vitamin E quinone and ubiquinone, generating antioxidant forms of these molecules. NQO1 has recently been shown to interact with superoxide and may be involved in scavenging superoxide within the cell. In addition, the possible role of NQO1 in p53 stabilization and consequently in contributing to p53-dependent stress responses is summarized. Such protein multitasking is a good strategy in terms of cellular economy. NQO1 can also be exploited in the design of NQO1-directed antitumor agents such as the new aziridinylbenzoquinone RH1 and Hsp90 inhibitors such as 17AAG. Polymorphisms in NQO1 which have profound influence on phenotype such as the NQO1*2 polymorphism may influence the chemoprotective actions of NQO1, and should be considered when NQO1-directed antitumor quinones are used for therapy in patients.