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Physiological Functions and Pathological Significance of NADPH Oxidase 3

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NADPH Oxidases Revisited: From Function to Structure

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Abstract

NADPH oxidase 3 (NOX3) is the catalytic subunit of a superoxide-producing enzyme complex in the inner ear. Other subunits of this complex include p22phox and NOX organizer 1 (NOXO1). Both of these accessory proteins are essential for the enzymatic activity of NOX3, with p22phox stabilizing, and NOXO1 activating it. In mice, deleterious mutations in the genes that encode any of these subunits cause a balance defect and a complete lack of calcium carbonate crystals (otoconia) in the gravity-sensing organs (utricle and saccule) of the inner ear. Consistent with a role in the genesis of otoconia, the NOX3-containing enzyme complex is expressed adjacent to the utricle and saccule, in the endolymphatic sac and duct. NOX3 and p22phox are also expressed in the cochlea, and NOX3 is likely enzymatically active and pathogenic at this location because inactivating mutations protect mice from distinct types of acquired hearing loss. Thus, NOX3 plays both developmental and pathological roles in the inner ear. Finally, a few studies have linked NOX3 to physiological and pathological processes outside the inner ear. In this chapter we summarize key discoveries related to the expression pattern, interacting partners, physiological functions, and pathological effects of NOX3.

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Acknowledgments

We thank Dr. Christine Blaumueller for critical review of the manuscript. This project was supported by a grant from the National Institute on Deafness and Other Communication Disorders (https://www.nih.gov/R01DC014953 to B Bánfi) and by resources of the Iowa City Department of Veterans Affairs Medical Center.

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Authors and Affiliations

  1. Department of Anatomy and Cell Biology, Carver College of Medicine, University of Iowa, Iowa City, IA, USA

    Yoko Nakano & Botond Bánfi

  2. Inflammation Program, Carver College of Medicine, University of Iowa, Iowa City, IA, USA

    Yoko Nakano & Botond Bánfi

  3. Department of Otolaryngology – Head and Neck Surgery, Carver College of Medicine, University of Iowa, Iowa City, IA, USA

    Botond Bánfi

  4. Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, IA, USA

    Botond Bánfi

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  1. Yoko Nakano
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Correspondence to Botond Bánfi .

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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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Nakano, Y., Bánfi, B. (2023). Physiological Functions and Pathological Significance of NADPH Oxidase 3. In: Pick, E. (eds) NADPH Oxidases Revisited: From Function to Structure. Springer, Cham. https://doi.org/10.1007/978-3-031-23752-2_11

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