ROLE OF NITRIC-OXIDE IN CELL RESPIRATION

Role of nitric oxide in cell respiration. Nitric oxide (NO) synthesize d in a constitutive manner by a cell, acts on effector cells as a phys iological regulator of the vascular tone, of platelet inhibition and o f neuron-neuron interaction. By contrast, the release for longer perio ds of time of higher amounts of inducible NO, transforms NO from a phy siological mediator into a cytostatic and cytotoxic molecule. The pres ence of NO synthetase in mitochondria suggests that physiological smal l amounts of NO could be involved in cellular respiration regulation b y inhibition of cytochrome oxidase. Long exposure of cells to NO resul ts in an irreversible inhibition of cellular respiration not dependent on a generalized superoxide or peroxynitrite formation. Cellular resp iration inhibition could be reverted by either analyzing complex IV al one, by blocking Complex I or by the addition of gluthation. Therefore , our hypothesis is that suppression of complex IV is a normal physiol ogical effect dependent on NO concentration. When cells are exposed to NO for longer periods of time, thiol groups are nitrosilated in compl ex I while gluthation transnitrosilates until its level drops to criti cal values. At this point, cellular respiration is blocked and this co uld be the pathway by which NO is transformed from a physiological med iator into a pathological molecule. We also believe that thiol nitrosi lation and transnitrosilation by gluthation is a critical mechanism in volved in oxidative stress prevention.