Editorial Endosomal ClC-3 and Nox1 Moving Marksmen of Redox Signaling?

Despite tremendous advances in our knowledge of therole of oxidative species in vascular disease, much debate remains regarding the mechanism by which NADPH oxidases (Nox) impart specific effects in cells. Over the past 2 decades, the term oxidative stress has often been used to describe the effects of Nox-derived reactive oxygen species (ROS). Much credence was initially given to relatively large quantities of ROS as mediators of myriad and varied cellular responses, ranging from connective tissue expression to differentiation, hypertrophy, proliferation, and apoptosis.1 With the discovery of multiple Nox isoforms and emergence of loss-of-function and gain-of-function technologies manip-ulating the levels of individual isoforms, a large body of literature emerged suggesting that small, localized ROS derived from individual Nox proteins can impart unique cellular responses. The lack of sophisticated detection meth