Cross talk between mitochondria and superoxide generating NADPH oxidase in breast and ovarian tumors.

Reactive oxygen species (ROS) signal cascades involved in cell growth, cell death, mitogenesis, angiogenesis and carcinogenesis. ROS are produced as a byproduct of oxidative phosphorylation (OXPHOS) in the mitochondria. It is estimated that 2–4% of the oxygen consumed during OXPHOS is converted to ROS. Besides mitochondria, NADPH-oxidase 1 (Nox1) also generates a significant amount of ROS in the cell. In this paper, we tested the hypothesis that mitochondria control Nox 1 redox signaling and the loss of control of this signaling contributes to tumorigenesis. We analyzed Nox1 expression in a mitochondrial gene knockout (?0) cell line and in the isogenic cybrid cell line in which mitochondrial genes were restored by transfer of wild type mitochondria into ?0 cells. Our study revealed, for the first time, that the inactivation of mitochondrial genes leads to down-regulation of Nox1 and that the transfer of wild type mitochondrial genes restores the Nox1 expression to a level comparable to that in the parenta...