Mitochondrial respiratory chain complex I is inactivated by NADPH oxidase Nox4

Reactive oxygen species (ROS) generated by NADPH oxidases play an important role in cellular signal transduction regulating cell proliferation, survival and differentiation. NADPH oxidase 4 (Nox4) induces cellular senescence in human endothelial cells; however, intracellular targets for Nox4 remained elusive. Here we show that Nox4 induces mitochondrial dysfunction in human endothelial cells. Nox4 depletion induced alterations in mitochondrial morphology, stabilized mitochondrial membrane potential, and decreased production of hydrogen peroxide in mitochondria. High-resolution respirometry in permeabilized cells combined with native polyacrylamide gel electrophoresis demonstrated that Nox4 specifically inhibits the activity of mitochondrial electron transport chain complex I, and this was associated with a decreased concentration of complex I subunits. These data suggest a new pathway by which sustained Nox4 activity decreases mitochondrial function.

Source: BJ Cell - March 20, 2013 Category: Biochemistry Authors: R Koziel, H Pircher, M Kratochwil, B Lener, M Hermann, N A Dencher, P Jansen-Dürr Tags: BJ Cell Source Type: research