Document Detail

Direct evidence for S-nitrosation of mitochondrial complex I.
MedLine Citation:
PMID:  16371007     Owner:  NLM     Status:  MEDLINE    
NO* (nitric oxide) is a pleiotropic signalling molecule, with many of its effects on cell function being elicited at the level of the mitochondrion. In addition to the well-characterized binding of NO* to the Cu(B)/haem-a3 site in mitochondrial complex IV, it has been proposed by several laboratories that complex I can be inhibited by S-nitrosation of a cysteine. However, direct molecular evidence for this is lacking. In this investigation we have combined separation techniques for complex I (blue-native gel electrophoresis, Superose 6 column chromatography) with sensitive detection methods for S-nitrosothiols (chemiluminescence, biotin-switch assay), to show that the 75 kDa subunit of complex I is S-nitrosated in mitochondria treated with S-nitrosoglutathione (10 microM-1 mM). The stoichiometry of S-nitrosation was 7:1 (i.e. 7 mol of S-nitrosothiols per mol of complex I) and this resulted in significant inhibition of the complex. Furthermore, S-nitrosothiols were detected in mitochondria isolated from hearts subjected to ischaemic preconditioning. The implications of these results for the physiological regulation of respiration, for reactive oxygen species generation and for a potential role of S-nitrosation in cardioprotection are discussed.
Lindsay S Burwell; Sergiy M Nadtochiy; Andrew J Tompkins; Sara Young; Paul S Brookes
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  The Biochemical journal     Volume:  394     ISSN:  1470-8728     ISO Abbreviation:  Biochem. J.     Publication Date:  2006 Mar 
Date Detail:
Created Date:  2006-02-22     Completed Date:  2006-07-28     Revised Date:  2013-06-07    
Medline Journal Info:
Nlm Unique ID:  2984726R     Medline TA:  Biochem J     Country:  England    
Other Details:
Languages:  eng     Pagination:  627-34     Citation Subset:  IM    
Department of Anesthesiology, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14620, USA.
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MeSH Terms
Electron Transport Complex I / metabolism*
Ischemic Preconditioning, Myocardial
Mitochondria / chemistry*,  metabolism*
Myocardium / metabolism
Nitrates / metabolism*
Rats, Sprague-Dawley
S-Nitrosothiols / metabolism
Sensitivity and Specificity
Grant Support
Reg. No./Substance:
0/Nitrates; 0/S-Nitrosothiols; EC Transport Complex I
Comment In:
Biochem J. 2008 Jun 1;412(2):e11-3   [PMID:  18466111 ]

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