FIG. 2.
Production of superoxide anion and hydrogen peroxide by the inhibition of mitochondrial oxygen uptake. (A) Inverse relationship between oxygen utilization and superoxide formation in mitochondria. The inverse relationship between superoxide production and residual Complex I activity is shown in fibroblasts of patients with isolated Complex I deficiency—Measurement of superoxide production was performed with hydroethydine in an inverted fluorescence microscope. Fluorescence intensity in the indicated compartment (left y-axis) is expressed as percentage of vehicle-treated control (CT). Closed and open symbols represent patient cell lines with a known (13 patients) and hitherto unknown (8 patients) as mutation, respectively. Linear regression analysis reveals an inverse correlation between superoxide production and residual CI activity for the whole cohort of patient cell lines. Reprinted from Verkaart et al. (224). © 2007 by Elsevier. (B) Effects of NO on electron transfer rate and hydrogen peroxide production. The effects of NO result in the inhibition of mitochondrial respiratory rate with an inverse increase of mitochondrial H2O2 yield, the product of dismutation of 
. The trace was obtained by simultaneous polarographic determinations of O2 utilization and fluorometric detection of H2O2, in rat heart submitochondrial particles (reproduced from Poderoso et al.) (182). © Elsevier, 1996. CI, confidence interval.