Regulation of novel superoxide-producing NAD(P)H oxidases.

Deliberate production of reactive oxygen species (ROS) are catalyzed by enzymes that belong to the NAD(P)H oxidase (Nox) family. The human genome contains seven members of the Nox family: the superoxide-producing enzymes Nox1 through Nox5 and the dual oxidases Duox1 and Duox2 that release hydrogen peroxide but not superoxide. Among them, the classical member gp91( phox )/Nox2 functions as the phagocyte NADPH oxidase, playing a crucial role in host defense. Although Nox2, heterodimerized with its membrane-spanning partner p22( phox ), is inactive in resting cells, during phagocytosis it forms an active complex with soluble regulatory proteins such as the organizer p47( phox ), the activator p67( phox ), and the small GTPase Rac. Here the authors describe how the novel superoxide-producing Nox oxidases (Nox1, 3, 4, and 5) with different functions are regulated by p22( phox ), the Nox organizers, the Nox activators, and Rac, and how their expression is controlled at the transcriptional level.