The study identifies Renox, a NAD(P)H oxidase in the kidney, as a potential oxygen sensor. Renox is homologous to gp91phox, a subunit of the phagocytic NADPH oxidase, and contains structural motifs essential for binding heme, flavin, and nucleotide. Renox is highly expressed in the renal cortex, particularly in proximal convoluted tubule epithelial cells, where it produces superoxide anions. Overexpression of Renox in NIH 3T3 fibroblasts increases superoxide production and leads to cellular senescence. These findings suggest that Renox may serve as a renal source of reactive oxygen species (ROS) involved in oxygen-dependent gene expression and inflammatory processes in the kidney. ROS play a central role in various physiological and pathological processes. In phagocytic cells, ROS are produced by the NADPH oxidase complex, which includes gp91phox. Other mammalian homologues of gp91phox, such as Mox1 and p138Tox, have been identified, but their functions remain unclear. The study also highlights the role of Renox in oxygen sensing, as it is expressed in the renal cortex where erythropoietin (EPO) is produced. EPO synthesis is regulated by oxygen levels, with superoxide anions and their downstream ROS intermediates forming in proportion to local oxygen concentrations. These ROS destabilize the transcription factor HIF-1α, decreasing EPO expression under hypoxia. Renox is expressed in the kidney but not in other tissues, and its expression is highest in the proximal convoluted tubule cells. In situ hybridization experiments confirmed this expression pattern. Renox overexpression in NIH 3T3 fibroblasts leads to increased superoxide production and cellular senescence, suggesting a role in ROS-mediated cellular processes. The study also notes that Renox may be involved in kidney diseases due to its role in ROS production, which can cause tissue injury and inflammatory responses. The identification of Renox as a renal NAD(P)H oxidase provides new insights into oxygen sensing and its regulation of EPO synthesis. Further research is needed to fully understand Renox's physiological and pathological roles, including its potential as a therapeutic target for diseases involving EPO deficiency.The study identifies Renox, a NAD(P)H oxidase in the kidney, as a potential oxygen sensor. Renox is homologous to gp91phox, a subunit of the phagocytic NADPH oxidase, and contains structural motifs essential for binding heme, flavin, and nucleotide. Renox is highly expressed in the renal cortex, particularly in proximal convoluted tubule epithelial cells, where it produces superoxide anions. Overexpression of Renox in NIH 3T3 fibroblasts increases superoxide production and leads to cellular senescence. These findings suggest that Renox may serve as a renal source of reactive oxygen species (ROS) involved in oxygen-dependent gene expression and inflammatory processes in the kidney. ROS play a central role in various physiological and pathological processes. In phagocytic cells, ROS are produced by the NADPH oxidase complex, which includes gp91phox. Other mammalian homologues of gp91phox, such as Mox1 and p138Tox, have been identified, but their functions remain unclear. The study also highlights the role of Renox in oxygen sensing, as it is expressed in the renal cortex where erythropoietin (EPO) is produced. EPO synthesis is regulated by oxygen levels, with superoxide anions and their downstream ROS intermediates forming in proportion to local oxygen concentrations. These ROS destabilize the transcription factor HIF-1α, decreasing EPO expression under hypoxia. Renox is expressed in the kidney but not in other tissues, and its expression is highest in the proximal convoluted tubule cells. In situ hybridization experiments confirmed this expression pattern. Renox overexpression in NIH 3T3 fibroblasts leads to increased superoxide production and cellular senescence, suggesting a role in ROS-mediated cellular processes. The study also notes that Renox may be involved in kidney diseases due to its role in ROS production, which can cause tissue injury and inflammatory responses. The identification of Renox as a renal NAD(P)H oxidase provides new insights into oxygen sensing and its regulation of EPO synthesis. Further research is needed to fully understand Renox's physiological and pathological roles, including its potential as a therapeutic target for diseases involving EPO deficiency.