Surface oxidase and oxidative stress propagation in aging

This report summarizes new evidence for a plasmamembrane-associated hydroqu inone oxidase designated as CNOX (constitutive plasma membrane NADH oxidase ) that functions as a terminal oxidase for a plasma membrane oxidoreductase (PMOR) electron transport chain to link the accumulation of lesions in mit ochondrial DNA to cell-surface accumulations of reactive oxygen species. Pr evious considerations of plasma membrane redox changes during aging have la cked evidence for a specific terminal oxidase to catalyze a flow of electro ns from cytosolic NADH to molecular oxygen (or to protein disulfides), Cell s with functionally deficient mitochondria become characterized by an anaer obic metabolism, As a result, NADH accumulates from the glycolytic producti on of ATP, Elevated PMOR activity has been shown to be necessary to maintai n the NAD(+)/ADH homeostasis essential for survival, Our findings demonstra te that the hyperactivity of the PMOR system results in an NADH oxidase (NO X) activity capable of generating reactive oxygen species at the cell surfa ce. This would serve to propagate the aging cascade both to adjacent cells and to circulating blood components. The generation of superoxide by NOX fo rms associated with aging is inhibited by coenzyme Q and provides a rationa l basis for the anti-aging activity of circulating coenzyme Q.