Complex I specific increase in superoxide formation and respiration rate by PrP-null mouse brain mitochondria.
An imbalance in free radical production and removal is considered by many to be an important factor in the etiology of many degenerative diseases. Since mitochondria are a major source of free radicals, we have examined mitochondrial free radical production in relation to oxidative phosphorylation in PrP-null mice. Quantitative electron paramagnetic resonance spectroscopy revealed up to a 70% increase in superoxide production from Complex I of submitochondrial particles prepared from PrP-null mice. This was accompanied by elevated respiratory capacity through Complex I without any discernible alteration in respiratory efficiency. These differences are associated with changes in superoxide dismutase levels and defects in mitochondrial morphology, confirming previously reported results. Our results demonstrate a clear difference in free radical production and oxygen consumption by mitochondrial Complex I between PrP-null mice and wild-type controls, pointing to Complex I as a potential target for pathological change, suggesting similarities between prion-related and other neurodegenerative diseases.
Paterson
Andrew W J
AW
Centre for Integrative Physiology, Hugh Robson Building, George Square, Edinburgh, UK.
Curtis
John C
JC
Macleod
Nikki K
NK
D000367:Age Factors; D000818:Animals; D001921:Brain / Q000648:ultrastructure*; D019069:Cell Respiration / Q000502:physiology; D004578:Electron Spin Resonance Spectroscopy / Q000379:methods; D042967:Electron Transport Complex I / Q000378:metabolism*; D005609:Free Radicals / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission / Q000379:methods; D008928:Mitochondria / Q000502:physiology*; D010101:Oxygen Consumption / Q000502:physiology; D011328:Prions / Q000235:genetics*; D013367:Submitochondrial Particles / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism*; D050995:Voltage-Dependent Anion Channel 1 / Q000378:metabolism
D005609:Free Radicals; D011328:Prions; D013481:Superoxides; D050995:Voltage-Dependent Anion Channel 1; D042967:Electron Transport Complex I