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Reversible inhibition of cytochrome c oxidase, the terminal enzyme of the mitochondrial respiratory chain, by nitric oxide
Author(s) -
Cleeter M.W.J.,
Cooper J.M.,
Darley-Usmar V.M.,
Moncada S.,
Schapira A.H.V.
Publication year - 1994
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(94)00424-2
Subject(s) - nitric oxide , cytochrome c oxidase , respiratory chain , mitochondrial respiratory chain , chemistry , mitochondrion , cytochrome c , biochemistry , cytochrome , enzyme , nitric oxide synthase , organic chemistry
Incubation of rat skeletal muscle mitochondria with the nitric oxide generator, S ‐nitrosoglutathione (GSNO) reversibly inhibited oxygen utilisation with all substrates tested. The visible absorption spectra of the inhibited mitochondria showed that cytochromes c + c 1 , b and a + a 3 were reduced, indicating a block at the distal end of the respiratory chain. Analysis of the respiratory chain enzyme activities in the presence of GSNO localised the site of inhibition to cytochrome c oxidase alone. These results indicate that nitric oxide is capable of rapidly and reversibly inhibiting the mitochondrial respiratory chain and may be implicated in the cytotoxic effects of nitric oxide in the CNS and other tissues.