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DUOX1 and DUOX2, DUOXA1 and DUOXA2

par Miot, Françoise ;De Deken, Xavier
Référence NADPH Oxidases Revisited: From Function to Structure, Springer International Publishing, page (229-245)
Publication Publié, 2023

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Résumé :

DUOX1 and DUOX2 constitute a subgroup of long ($sim$1500 amino acids) seven transmembrane domain NADPH oxidases. In addition to the catalytic core com- mon to NOX1–5, comprising NADPH- and FAD-binding sites, heme arrangement for electron transfer from NADPH across the membrane to O2, they possess a N-terminal extracellular peroxidase homologous domain followed by an intracellular loop with two Ca++ EF-hand binding sites. They produce H2O2 extracellularly when correctly processed with their DUOXA at the plasma membrane of the cell. DUOX1 and 2 were initially isolated from the thyroid. DUOX/DUOXA complexes produce H2O2 required as co-substrate for the thyroperoxidase involved in thyroid hormone synthesis. DUOX2 and to a lesser extent DUOXA2 genes are fre- quently mutated and non-functional variants are fre- quently associated with congenital hypothyroidism, but with variable penetrance and hypothyroid phenotypes ranging from transient to permanent hypothyroidism and partial to total iodide organification defect. DUOX1 and 2 are also expressed on epithelial surfaces of the airways, salivary gland ducts and DUOX2 along the gastrointesti- nal digestive tract. Associated with lactoperoxidase, they constitute an efficient host defense mechanism against bacterial and viral infections. In the gut, DUOX2 is robustly induced to neutralize microbial proliferation and to maintain immune homeostasis. Deleterious variants of DUOX2 associated with congenital hypothyroidism could therefore increase the susceptibility to develop inflammatory bowel disease.