Figure 3.

Structure of NADPH oxidase in the heart. NADPH oxidase complex is composed of two major components. Plasma membrane spanning cytochrome b558 composed of p22phox and a Nox subunit (gp91phox (Nox2), Nox4) and cytosolic components composed of four regulatory subunits (p47 phox, p67 phox, p40 phox and Rac1). The low molecular weight G protein rac1 participates in assembly of the active complex. Upon activation, cytosolic components interact with cytochrome b558 to form an active NADPH oxidase enzyme complex, resulting in release of ·O₂⁻. The primary Nox subunit isoforms in cardiac cells are Nox2 and Nox4. Nox4 oxidase localizes intracellular organelles around the nucleus. The activity of Nox4 results in the direct release of hydrogen peroxide (H₂O₂) in mitochondria. The mechanisms underlying the generation of hydrogen peroxide by Nox4 oxidase are yet to be fully characterized.