Elevated neuronal nitric oxide synthase expression during ageing and mitochondrial energy production.
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.
Pharmacology & Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, CA 90089, USA.
Philip Y
PY
Lam
Fei
F
Yin
Ryan T
RT
Hamilton
Alberto
A
Boveris
Enrique
E
Cadenas
D000375:Aging / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000378:metabolism*; D015256:Coenzyme A-Transferases / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D004734:Energy Metabolism; D008297:Male; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism; D025261:Mitochondrial Proton-Translocating ATPases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009566:Nitrates / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I; D011499:Protein Processing, Post-Translational; D051381:Rats; D011916:Rats, Inbred F344; D026361:Reactive Nitrogen Species / Q000378:metabolism; D053719:Tandem Mass Spectrometry; D014443:Tyrosine / Q000737:chemistry
D024101:Mitochondrial Proteins; D009419:Nerve Tissue Proteins; D009566:Nitrates; D026361:Reactive Nitrogen Species; D014443:Tyrosine; D045304:Cytochromes c; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat; D015256:Coenzyme A-Transferases; C021460:3-ketoacid CoA-transferase; D025261:Mitochondrial Proton-Translocating ATPases