Subcellular localization of Nox4 and regulation in diabetes

• DOI: 10.1073/pnas.0906805106
• Publication Date: 2009-08-18T02:11:52Z
• Authors: Karen Block; Yves Gorin; Hanna E. Abboud
• Keywords: NOX4

Oxidative stress is implicated in human diseases. Some of the oxidative pathways are harbored mitochondria. NAD(P)H oxidases have been identified not only phagocytic but also somatic cells. Nox4 most ubiquitous these and a major source reactive oxygen species (ROS) many cell types kidney tissue diabetic animals. We generated specific antibodies, found that localizes to (i) Immunoblot analysis cultured mesangial cells cortex revealed present crude mitochondria, mitochondria-enriched heavy fractions, purified mitochondria; (ii) immunofluorescence confocal microscopy with mitochondrial marker Mitotracker; (iii) localization prediction program MitoProt indicated probability score for identical protein cytochrome c oxidase subunit IV. show siRNA-mediated knockdown significantly reduces NADPH activity pure mitochondria blocks glucose-induced superoxide generation. In rat model diabetes, expression increased cortex. Our data provide evidence functional regulated indicating existence previously undescribed ROS this organelle.