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Complex I specific increase in superoxide formation and respiration rate by PrP‐null mouse brain mitochondria
Author(s) -
Paterson Andrew W. J.,
Curtis John C.,
MacLeod Nikki K.
Publication year - 2008
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2007.05123.x
Subject(s) - respiration , mitochondrion , superoxide
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.