Cytochrome oxidase nitric oxide complex

The property of NO of inhibiting mitochondrial electron transfer was first recognized in 1994 by two British research groups [14, 15] that reported the inhibition of brain and muscle cytochrome oxidase (complex IV) activity by low NO concentrations in a reversible and Oj-competitive manner. More related to the scope of this review is the NO inhibition of electron transfer at complex III, ubiquinol-cytochrome c reductase, the second NO-sensitive point in the respiratory chain, where inhibition of electron transfer between cytochromes b and c enhances mitochondrial H2O2 production [16]. Nitric oxide, produced by NO donors or by mitochondrial nitric oxide synthase (mtNOS), inhibits complex III electron transfer and increases Oy and H2O2 production in sub-mitochondrial particles and in mitochondria. Complex IV is more sensitive to NO inhibition (IC5o=O.l pM) than complex III (IC5o=O.2 pM). 

In addition to cytochrome c oxidase, a protein complex having a very similar fold and arrangement of metal centers is that of the heme-containing nitric oxide reductase (NOR). This protein complex is found in a number of anaerobic bacteria and archaea, including Para coccus cfe/ /7/i5cans, Bacillus azotoformans and Pyrobaculum sero/ Mu/w, and carries out the enzy matic reaction 2NO + 2e + 2H+ = N2O + H2O. (Although this is only a 2-electron reduction, NORs can also reduce O2 to 2H2O, a 4-electron reduction, and at least several CcOs can reduce 2NO to N2O + H2O, a... 

Nitric oxide decreases oxygen consumption, and the effect is incremental with hypoxia (21,22). This inhibition appears to result firom S-nitrosylation of the critical thiol group in complex IV of cytochrome oxidase and is immediately reversed by exposure to high-intensity light (23). This is analogous to CO effects on the respiratory chain (2,3,24), and this presumably is the basis of O2 sensing by NO. 

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