title: Complex I specific increase in superoxide formation and respiration rate by PrP-null mouse brain mitochondria.
abstract: 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.
authors.affiliation: Centre for Integrative Physiology, Hugh Robson Building, George Square, Edinburgh, UK.
authors.forename: Andrew W J
authors.initials: AW
authors.lastname: Paterson
authors.forename: John C
authors.initials: JC
authors.lastname: Curtis
authors.forename: Nikki K
authors.initials: NK
authors.lastname: Macleod
mesh_terms: 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
chemical_list: D005609:Free Radicals; D011328:Prions; D013481:Superoxides; D050995:Voltage-Dependent Anion Channel 1; D042967:Electron Transport Complex I