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Persistent inhibition of cell respiration by nitric oxide: crucial role of S-nitrosylation of mitochondrial complex I and protective action of glutathione

Clementi, Emilio, Brown, Guy Charles, Feelisch, Martin and Moncada, Salvador (1998) Persistent inhibition of cell respiration by nitric oxide: crucial role of S-nitrosylation of mitochondrial complex I and protective action of glutathione Proceedings of the National Academy of Sciences, 95, (13), pp. 7631-7636. (PMID:9636201).

Record type: Article

Abstract

Both reversible and irreversible inhibition of mitochondrial respiration have been reported following the generation of nitric oxide (NO) by cells. Using J774 cells, we have studied the effect of long-term exposure to NO on different enzymes of the respiratory chain. Our results show that, although NO inhibits complex IV in a way that is always reversible, prolonged exposure to NO results in a gradual and persistent inhibition of complex I that is concomitant with a reduction in the intracellular concentration of reduced glutathione. This inhibition appears to result from S-nitrosylation of critical thiols in the enzyme complex because it can be immediately reversed by exposing the cells to high intensity light or by replenishment of intracellular reduced glutathione. Furthermore, decreasing the concentration of reduced glutathione accelerates the process of persistent inhibition. Our results suggest that, although NO may regulate cell respiration physiologically by its action on complex IV, long-term exposure to NO leads to persistent inhibition of complex I and potentially to cell pathology.

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More information

Published date: 23 June 1998
Organisations: Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 337887
URI: http://eprints.soton.ac.uk/id/eprint/337887
ISSN: 0027-8424
PURE UUID: 85dc23b0-74de-4b60-8c77-64960395840b
ORCID for Martin Feelisch: ORCID iD orcid.org/0000-0003-2320-1158

Catalogue record

Date deposited: 29 Jun 2012 13:13
Last modified: 18 Jul 2017 06:00

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Contributors

Author: Emilio Clementi
Author: Guy Charles Brown
Author: Martin Feelisch ORCID iD
Author: Salvador Moncada

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