The gp91 ^phox Component of NADPH Oxidase Is Not a Voltage-gated Proton Channel

During the “respiratory burst” in phagocytes, NADPH oxidase helps kill microbes by producing superoxide anion, O₂⁻. As illustrated in the cartoon in Fig. 1, the NADPH oxidase complex has several components. In unstimulated cells, four components (p67^phox, p40^phox, p47^phox, and a G protein, Rac) are located in the cytosol, and gp91^phox and p22^phox are membrane bound. Upon stimulation by bacteria, PMA (phorbol ester), or chemotactic peptides, the complex assembles and begins to generate O₂⁻. This is accomplished by transporting electrons from NADPH inside the cell, across the cell membrane to reduce extracellular O₂ to O₂⁻. Without charge compensation, the electron efflux in a human eosinophil would depolarize the membrane by ∼12 V/s, and this opposing voltage would shut down the oxidase within ∼20 ms. Henderson et...