Nitric oxide inhibition of mitochondrial respiration and its role in cell death.
Nitric oxide (NO) or its derivatives (reactive nitrogen species, RNS) inhibit mitochondrial respiration in two different ways: (i) an acute, potent, and reversible inhibition of cytochrome oxidase by NO in competition with oxygen; and, (ii) irreversible inhibition of multiple sites by RNS. NO inhibition of respiration may impinge on cell death in several ways. Inhibition of respiration can cause necrosis and inhibit apoptosis due to ATP depletion, if glycolysis is also inhibited or is insufficient to compensate. Inhibition of neuronal respiration can result in excitotoxic death of neurons due to induced release of glutamate and activation of NMDA-type glutamate receptors. Inhibition of respiration may cause apoptosis in some cells, while inhibiting apoptosis in other cells, by mechanisms that are not clear. However, NO can induce (and inhibit) cell death by a variety of mechanisms unrelated to respiratory inhibition.
Brown
Guy C
GC
Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom. gcb@mole.bio.cam.ac.uk
Borutaite
Vilmante
V
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D016923:Cell Death; D003576:Electron Transport Complex IV / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000378:metabolism* / Q000473:pathology; D008954:Models, Biological; D009336:Necrosis; D009474:Neurons / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism*; D010101:Oxygen Consumption; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism
D016194:Receptors, N-Methyl-D-Aspartate; D009569:Nitric Oxide; D000255:Adenosine Triphosphate; D003576:Electron Transport Complex IV