Mitochondrial nitric oxide synthase (mtNOS), a voltage-dependent enzyme, is responsible for NO diffusion to cytosol

VALDEZ LB; BOVERIS A

Davos, Switzerland

Congreso; XIII Biennial Meeting of the Society for Free Radical Research International; 2006

Society for Free Radical Research International

It had been recognized that mitochondria release NO to the reaction medium; however, the relationship between NO release rates and mitochondrial energetic are not clear. The aim of this work was to determine the rates of NO release in mitochondrial metabolic states 4 and 3 and their relationship with membrane potential. The used methods have been described by Valdez et al. (2006). NO release was about 45% lower in state 3 than in state 4. The activity of mtNOS, responsible for NO release, is driven by membrane potential and not by intramitochondrial pH changes. NO release was exponentially dependent on membrane potential as reported for mitochondrial H2O2 production by Korshunov and co-workers. The regulation of mtNOS activity by membrane potential is marked at the physiological range of potentials. The intramitochondrial concentrations of L-arginine and NADPH are higher than their KM values, and the changes in their concentrations in the state 4-state 3 transition are not enough to explain the changes in NO release. These data indicate that the redox state of the respiratory chain components regulates H2O2 production and membrane potential modulates NO release, and support the speculation that NO and H2O2 report a high mitochondrial energy charge to the cytosol.