[Role of nitric oxide in cell respiration]

Nitric oxide (NO) synthesized in a constitutive manner by a cell, acts on effector cells as a physiological regulator of the vascular tone, of platelet inhibition and of neuron-neuron interaction. By contrast, the release for longer periods of time of higher amounts of inducible NO, transforms NO from a physiological mediator into a cytostatic and cytotoxic molecule. The presence of NO synthetase in mitochondria suggests that physiological small amounts of NO could be involved in cellular respiration regulation by inhibition of cytochrome oxidase. Long exposure of cells to NO results in an irreversible inhibition of cellular respiration not dependent on a generalized superoxide or peroxynitrite formation. Cellular respiration inhibition could be reverted by either analyzing complex IV alone, by blocking Complex I or by the addition of gluthation. Therefore, our hypothesis is that suppression of complex IV is a normal physiological effect dependent on NO concentration. When cells are exposed to NO for longer periods of time, thiol groups are nitrosilated in complex I while gluthation transnitrosilates until its level drops to critical values. At this point, cellular respiration is blocked and this could be the pathway by which NO is transformed from a physiological mediator into a pathological molecule. We also believe that thiol nitrosilation and transnitrosilation by gluthation is a critical mechanism involved in oxidative stress prevention.