NADPH oxidase-derived reactive oxygen species: Dosis facit venenum

Abstract

New findings: What is the topic of this review? Within this review, the role of reactive oxygen species in cellular homeostasis, physiology and pathophysiology is discussed. What advances does it highlight? The review provides new concepts of how reactive oxygen species influence gene expression, energy consumption and other aspects of the life of a cell. Furthermore, a model is provided to illustrate how reactive oxygen species elicit specific oxidation of target molecules.

Abstract: Reactive oxygen species (ROS) have a long history of bad reputation. They are needed and effective in host defense, but on the contrary may induce situations of oxidative stress. Besides that, within recent years several soft functions (functions that may occur and are not directly connected to an effect, but may influence signaling in an indirect manner) of NADPH oxidases have been discovered, which are slowly eroding the image of the solely dangerous ROS. NADPH oxidase-derived ROS serve to ease or enable signal transduction and to maintain homeostasis. However, there is still an enormous lag in the knowledge concerning target proteins and how ROS can elicit specific signalling in different cells and tissues. The present review summarizes some important functions of Nox2 and Nox4. Furthermore, although highly speculative, a model is provided of how those NADPH oxidases might be able to oxidize target proteins in a specific way. Many concepts mentioned in this review represent my personal view and are supported only in part by published studies.

Keywords: NADPH oxidases; Nox2; Nox4; ROS; reactive oxygen species; redox cloud.

Figure 1

The figure shows Nox4 together with p22phox in the endoplasmatic reticulum. Nox4 produces H₂O₂, which builds a ‘redox cloud’. A microtubule is passing the cloud, which enables transport proteins (e.g. kinesins) to bring target proteins into the redox surrounding. This eventually results in the oxidation of the target protein and its release from the transport protein. The oxidized target protein may then mediate redox signalling, control gene expression or could even be decomposed. The possibility of oxidized transport proteins or tubulin is not shown