Cited by 766Neutrophil, Myeloperoxidase and Oxidative MechanismsRedox biology and oxidative stressNitric Oxide and Endothelin Effects

NADPH Oxidases (NOX): An Overview from Discovery, Molecular Mechanisms to Physiology and Pathology

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Vermot, Annelise, Petit-Härtlein, Isabelle, Smith, Susan M. E., Fieschi, Franck·2021·Antioxidants

Abstract

The reactive oxygen species (ROS)-producing enzyme NADPH oxidase (NOX) was first identified in the membrane of phagocytic cells. For many years, its only known role was in immune defense, where its ROS production leads to the destruction of pathogens by the immune cells. NOX from phagocytes catalyzes, via one-electron trans-membrane transfer to molecular oxygen, the production of the superoxide anion. Over the years, six human homologs of the catalytic subunit of the phagocyte NADPH oxidase were found: NOX1, NOX3, NOX4, NOX5, DUOX1, and DUOX2. Together with the NOX2/gp91phox component present in the phagocyte NADPH oxidase assembly itself, the homologs are now referred to as the NOX family of NADPH oxidases. NOX are complex multidomain proteins with varying requirements for assembly with combinations of other proteins for activity. The recent structural insights acquired on both prokaryotic and eukaryotic NOX open new perspectives for the understanding of the molecular mechanisms inherent to NOX regulation and ROS production (superoxide or hydrogen peroxide). This new structural information will certainly inform new investigations of human disease. As specialized ROS producers, NOX enzymes participate in numerous crucial physiological processes, including host defense, the post-translational processing of proteins, cellular signaling, regulation of gene expression, and cell differentiation. These diversities of physiological context will be discussed in this review. We also discuss NOX misregulation, which can contribute to a wide range of severe pathologies, such as atherosclerosis, hypertension, diabetic nephropathy, lung fibrosis, cancer, or neurodegenerative diseases, giving this family of membrane proteins a strong therapeutic interest.

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  • NOx catalyzes the reduction reaction of O2 to •O2− and/or H2O2 using NADPH as an electron donor and is located extracellularly.

    “NOx catalyzes the reduction reaction of O2 to •O2− and/or H2O2 using NADPH as an electron donor and it is located extracellularly [88].”

    From The Role of Reactive Species on Innate Immunity (2022) · cites this paper as [88]

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Authors
Vermot, A., Petit-Härtlein, I., Smith, S. M. E., & Fieschi, F.
Affiliations
  • Centre National de la Recherche Scientifique (FR)
  • Kennesaw State University (US)
Corresponding author
Fieschi, Franck
Venue
Antioxidants
Publisher
MDPI AG
Published
2021-06-01
Volume
10
Issue
6
Pages
890
ISSN
2076-3921 (ISSN-L)
OpenAlex
W3168173367
Cited by
766
References
457
Citations by year
2026: 144 · 2025: 202 · 2024: 191 · 2023: 128 · 2022: 85 · 2021: 16
FWCI
10.75
Type
journal article
Language
en
Open access
Locations
  • Antioxidants (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DigitalCommons - Kennesaw State University (Kennesaw State University) (submittedVersion)
  • HAL (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Agence Nationale de la Recherche (ANR- 17-CE11-0013)
  • Univ. Grenoble Alpes (Emergence program)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
  • Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
Keywords
NADPH oxidase, reactive oxygen species, superoxide production, NOX1, NOX2, NOX3, NOX4, NADPH oxidase 5, DUOX1, DUOX2, gp91phox, phagocyte NADPH oxidase, superoxide dismutase, hydrogen peroxide, host defense, signal transduction, gene expression regulation, cell differentiation, atherosclerosis, hypertension, diabetic nephropathy, pulmonary fibrosis, cancer, neurodegenerative diseases, therapeutic target

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