Reversible inhibition of cytochrome c oxidase, the terminal enzyme of the mitochondrial respiratory chain, by nitric oxide. Implications for neurodegenerative diseases.

Abstract:

: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+c1, b and a+a3 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 of 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.

journal_name

FEBS Lett

journal_title

FEBS letters

authors

Cleeter MW,Cooper JM,Darley-Usmar VM,Moncada S,Schapira AH

doi

10.1016/0014-5793(94)00424-2

subject

Has Abstract

pub_date

1994-05-23 00:00:00

pages

50-4

issue

1

eissn

0014-5793

issn

1873-3468

pii

0014-5793(94)00424-2

journal_volume

345

pub_type

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