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Free Radic Res. 2009 May;43(5):431-9. doi: 10.1080/10715760902849813.

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

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1
Pharmacology & Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, CA 90089, USA.

Abstract

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.

PMID:
19347761
PMCID:
PMC3319075
DOI:
10.1080/10715760902849813
[Indexed for MEDLINE]
Free PMC Article
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