Elevated neuronal nitric oxide synthase expression during ageing and mitochondrial energy production

Philip Y. Lam, Fei Yin, Ryan T. Hamilton, Alberto Boveris, Enrique Cadenas

Research output: Contribution to journalArticlepeer-review

42 Scopus citations


This study evaluated the effect of ageing on brain mitochondrial function mediated through protein post-translational modifications. Neuronal nitric oxide synthase increased with age and this led to a discreet pattern of nitration of mitochondrial proteins. LC/MS/MS analyses identified the nitrated mitochondrial proteins as succinyl-CoA-transferase and F1-ATPase; the latter was nitrated at Tyr269, suggesting deficient ADP binding to the active site. Activities of succinyl-CoA-transferase, F1 -ATPase and cytochrome oxidase decreased with age. The decreased activity of the latter cannot be ascribed to protein modifications and is most likely due to a decreased expression and assembly of complex IV. Mitochondrial protein post-translational modifications were associated with a moderately impaired mitochondrial function, as indicated by the decreased respiratory control ratios as a function of age and by the release of mitochondrial cytochrome c to the cytosol, thus supporting the amplification of apoptotic cascades.

Original languageEnglish (US)
Pages (from-to)431-439
Number of pages9
JournalFree Radical Research
Issue number5
StatePublished - 2009
Externally publishedYes


  • Ageing
  • F-ATPase
  • Nitration
  • nNOS
  • Succinyl-CoA-transferase

ASJC Scopus subject areas

  • Biochemistry


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