Complex I specific increase in superoxide formation and respiration rate by PrP-null mouse brain mitochondria

Andrew W. J. Paterson, John C. Curtis, Nikki K. MacLeod

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)177-191
Number of pages15
JournalJournal of Neurochemistry
Volume105
Issue number1
DOIs
Publication statusPublished - Apr 2008

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