The gp91phox component of NADPH oxidase is not a voltage-gated proton channel

The preponderance of the evidence supports the idea that the voltage-gated proton channel is a separate entity from the NADPH oxidase complex. The idea that gp91phox is a proton channel should be abandoned. We have tested this hypothesis definitively (DeCoursey et al., 2001b; Morgan et al., 2002) and found no evidence to sustain it. Neither gp91phox nor any of its homologues has been demonstrated to function as a proton channel. On the contrary, expression of gp91phox does not result in H+ currents. Furthermore, all known components of H+ current in resting and activated phagocytes persist in cells lacking gp91phox. Because the molecular and genetic identity of the voltage-gated proton channel remains unknown, we still need to identify this molecule. Both NADPH oxidase and the H+ channel play important roles during the respiratory burst in phagocytes. Their interaction, regulation, modulation, expression, trafficking, and physiology are rich areas for future study.