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.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Aging / metabolism*
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Amino Acid Sequence
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Animals
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Brain / metabolism*
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Coenzyme A-Transferases / metabolism
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Cytochromes c / metabolism
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Energy Metabolism
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Male
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Mitochondria / metabolism*
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Mitochondrial Proteins / metabolism
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Mitochondrial Proton-Translocating ATPases / chemistry
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Mitochondrial Proton-Translocating ATPases / genetics
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Mitochondrial Proton-Translocating ATPases / metabolism
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Models, Molecular
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Molecular Sequence Data
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Nerve Tissue Proteins / metabolism
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Nitrates / metabolism
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Nitric Oxide Synthase / metabolism*
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Nitric Oxide Synthase Type I
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Protein Processing, Post-Translational
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Rats
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Rats, Inbred F344
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Reactive Nitrogen Species / metabolism
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Tandem Mass Spectrometry
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Tyrosine / chemistry
Substances
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Mitochondrial Proteins
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Nerve Tissue Proteins
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Nitrates
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Reactive Nitrogen Species
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Tyrosine
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Cytochromes c
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Nitric Oxide Synthase
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Nitric Oxide Synthase Type I
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Nos1 protein, rat
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Coenzyme A-Transferases
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3-ketoacid CoA-transferase
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Mitochondrial Proton-Translocating ATPases