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p47phox and NOXO1, the Organizer Subunits of the NADPH Oxidase 2 (Nox2) and NADPH Oxidase 1 (Nox1)

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NADPH Oxidases Revisited: From Function to Structure

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Abstract

The enzyme responsible for superoxide anion production in phagocytes is called the phagocyte NADPH oxidase. It is a multicomponent enzyme system resulting from the assembly upon activation of four cytosolic proteins (p47phox, p67phox, p40phox and Rac1 or Rac2) with two transmembrane proteins (p22phox and gp91phox, which form the cytochrome b558). The gp91phox is the catalytic subunit of the phagocyte NADPH oxidase and was the first NADPH oxidase to be discovered, renamed today as NOX2. Since then, a family of NOX enzymes, comprising NOX1 to NOX5 and the two DUOX, DUOX1 and DUOX2 has been characterized. NOX1 was the first homologue of gp91phox to be identified, and now refers to a multicomponent enzyme complex composed of three cytosolic proteins (NOXO1, a p47phox homologue, NOXA1, a p67phox homologue and Rac1) with two transmembrane proteins (NOX1 and p22phox). NOX1- and NOX2-derived ROS are essential for innate immunity and other physiological functions; however, excessive ROS production can induce tissue injury, contributing to inflammatory diseases. Thus, NOX1 and NOX2 activation must be tightly regulated in time and space in order to limit ROS production. p47phox and NOXO1 play a major role in the regulation and organization of the NOX2 and NOX1 complexes, respectively, through the interactions of specific protein domains and via phosphorylation. This chapter aims to provide new insights on the role of p47phox and NOXO1 in NOX2 and NOX1 regulation and activation.

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Acknowledgements

This work was supported by grants from Institut National de la Santé et de la Recherche Médicale (INSERM) and Centre National de la Recherche Scientifique (CNRS), Université Paris Diderot, le Labex Inflamex, et l’Association Vaincre la Mucoviscidose (VLM). The authors wish to thank Martine Torres, Ph.D. for her editorial assistance.

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  1. Pham My-Chan Dang and Jamel El-Benna contributed equally to this chapter.

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  1. Centre de Recherche sur l’Inflammation (CRI), INSERM-U1149, CNRS-ERL8252, Laboratoire d’Excellence Inflamex, Université de Paris, Faculté de Médecine Xavier Bichat, Paris, France

    Pham My-Chan Dang & Jamel El-Benna

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  1. Department of Clinical Microbiology and Immunology, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel

    Edgar Pick

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Dang, P.MC., El-Benna, J. (2023). p47phox and NOXO1, the Organizer Subunits of the NADPH Oxidase 2 (Nox2) and NADPH Oxidase 1 (Nox1). In: Pick, E. (eds) NADPH Oxidases Revisited: From Function to Structure. Springer, Cham. https://doi.org/10.1007/978-3-031-23752-2_15

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