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NADPH Oxidase 1: At the Interface of the Intestinal Epithelium and Gut Microbiota

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NADPH Oxidases Revisited: From Function to Structure

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Abstract

NOX1 was the first of the NOX family of NADPH oxidases described with sequence homologous to the well-known microbicidal NADPH oxidase of phagocytes. NOX1 not only shows close structural similarities with the phagocytic NOX2-based prototype, but also exhibits striking functional similarities as a regulated multi-component enzyme complex. Early studies explored proposed roles for NOX1 ranging from reactive oxygen species (ROS)-related signaling functions in responses to activated oncogenes, growth factors, and vascular agonists to voltage-gated proton transport. However, most current evidence supports notions of NOX1 functioning primarily in roles related to mucosal innate immunity, particularly in the colon epithelium where it exhibits its highest expression. Like its phagocytic counterpart, it acts as a tightly regulated ROS generator responsive to a variety of microbial patterns and induced by inflammatory cytokines. Defects in NOX1 in humans are associated with inflammatory bowel disease, consistent with roles of NOX1 related to innate immunity. Recent cancer transcriptomic analysis has not supported proposed links between high NOX1 expression and RAS mutations or cancer progression. This review provides an historical account of research developments on the NOX1-based NADPH oxidase and offers critical perspectives on these findings in the broader context of the redox biology field.

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Acknowledgments

This work was supported, in part, by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, NIH (T.L.L.). The research of M.G. is supported by a grant from the National Research, Development, and Innovation Office (K133002) and by grant VEKOP-2.3.2-16-2016-00002. His work is also supported by the Ministry of Innovation and Technology of Hungary from the National Research, Development and Innovation Fund, financed under the MOLORKIV funding scheme.

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  1. Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA

    Thomas L. Leto

  2. Faculty of Medicine, Department of Physiology, Semmelweis University, Budapest, Hungary

    Miklós Geiszt

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  2. Miklós Geiszt
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Correspondence to Thomas L. Leto .

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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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Leto, T.L., Geiszt, M. (2023). NADPH Oxidase 1: At the Interface of the Intestinal Epithelium and Gut Microbiota. In: Pick, E. (eds) NADPH Oxidases Revisited: From Function to Structure. Springer, Cham. https://doi.org/10.1007/978-3-031-23752-2_10

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