The PHOX-NOX family
The human genome encodes for seven NADPH oxidase (Nox)-like-systems that are transmembrane proteins involved in the electron transfer across membranes. Oxygen is the electron acceptor and is reduced to deliver superoxide anion O₂^– ,the electron donor is NADPH.
The phagocyte NADPH oxidase (Phox) was first identified in neutrophils as the enzyme responsible for the respiratory burst. The enzyme is dormant at resting but it is rapidly activated once the cells have been exposed to inflammatory stimuli. Activation of phox needs assembly of soluble regulatory components (p67-phox, p40-phox, p47-phox and Rac) with the membrane redox core of oxidase, called cytochrome b558. The hemoprotein is a 1/1 heterodimer made up of gp91-phox and p22-phox subunits.
Chronic granulomatous disease (CGD) is a rare hereditary disorder resulting from null oxidase activity. The susceptibility to infections of patients is due to the failure of neutrophils to generate O₂^–.
Other Nox members were shown to be expressed in many non phagocytic cells from which, fibroblasts, EBV-B lymphocytes, endothelial cells and chondrocytes ; but as opposed to phagocytes, the catalysed oxidase activity is very low. All these NADPH oxidase isoenzymes contain conserved binding sites for FAD, NADPH and hemes, and their N terminal domains contain a cluster of five hydrophobic segments that are predicted to form transmembrane helices.

Reactive oxygen species (ROS) generated from O₂^– and produced by the NADPH oxidases family, Nox, are at the core of inflammation and ageing. The GREPI tries to work out the role of the NOXs and to identify the targets of the oxidizing radicals produced during pathophysiological disorders. Among these targets, the emphasis refers to matrix metalloproteinases.