Nitric oxide and hypoxia.
NO (nitric oxide) can affect mitochondrial function by interacting with the cytochrome c oxidase (complex IV) of the electron transport chain in a manner that is reversible and in competition with oxygen. Concentrations of NO too low to inhibit respiration can trigger cell defence response mechanisms involving reactive oxygen species and various signalling molecules such as nuclear factor kappaB and AMP kinase. Inhibition of mitochondrial respiration by NO at low oxygen concentrations can cause so-called metabolic hypoxia and divert oxygen towards other oxygen-dependent systems. Such a diversion reactivates prolyl hydroxylases and thus accounts for the prevention by NO of the stabilization of hypoxia-inducible transcription factor. In certain circumstances NO interacts with superoxide radical to form peroxynitrite, which can affect the action of key enzymes, such as mitochondrial complex I, by S-nitrosation. This chapter discusses the physiological and pathophysiological implications of the interactions of NO with the cytochrome c oxidase.
Galkin
Alexander
A
The Wolfson Institute for Biomedical Research, The Cruciform Building, University College London, Gower Street, London WC1E 6BT, U.K.
Higgs
Annie
A
Moncada
Salvador
S
D000263:Adenylate Kinase / Q000378:metabolism; D000818:Animals; D004579:Electron Transport; D003576:Electron Transport Complex IV / Q000378:metabolism; D006801:Humans; D000860:Hypoxia; D008928:Mitochondria / Q000502:physiology; D008954:Models, Biological; D008956:Models, Chemical; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000737:chemistry / Q000378:metabolism*; D009584:Nitrogen / Q000737:chemistry; D010100:Oxygen / Q000737:chemistry; D020033:Protein Isoforms
D016328:NF-kappa B; D020033:Protein Isoforms; D009569:Nitric Oxide; D003576:Electron Transport Complex IV; D000263:Adenylate Kinase; D009584:Nitrogen; D010100:Oxygen