NADPH oxidase 4: walking the walk with Poldip2. Circ Res 105(3

Over the last decade, the NADPH oxidases have beenrecognized as an important source of reactive oxygen species (ROS) involved in both normal physiological redox-dependent processes, and in the generation of oxidative stress, with a role in the development of cardiovascular disease. As a multisubunit enzyme complex, the NADPH oxidases have the unusual composition of multiple interchange-able homologs of the catalytic, or NADPH oxidase (Nox), subunit that directly interacts with membrane-bound p22phox. It is at the Nox subunit that NADPH binding leads to electron transfer via heme groups to oxygen resulting in the generation of superoxide anion. Recent investigations have identified 7 dis-tinct Nox subunits, some possessing multiple splice variants, but the real challenge has been to characterize the specific cellular functions and the regulation of the various Nox enzymes. The difficulty in doing so is partly attributable to the presence o