Genetic variability of respiratory complex abundance, organization and activity in mouse brain

K. J. Buck, N. A.R. Walter, D. L. Denmark

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Mitochondrial dysfunction is implicated in the etiology and pathogenesis of numerous human disorders involving tissues with high energy demand. Murine models are widely used to elucidate genetic determinants of phenotypes relevant to human disease, with recent studies of C57BL/6J (B6), DBA/2J (D2) and B6xD2 populations implicating naturally occurring genetic variation in mitochondrial function/dysfunction. Using blue native polyacrylamide gel electrophoresis, immunoblots and in-gel activity analyses of complexes I, II, III, IV and V, our studies are the first to assess abundance, organization and catalytic activity of mitochondrial respiratory complexes and supercomplexes in mouse brain. Remarkable strain differences in supercomplex assembly and associated activity are evident, without differences in individual complexes I, II, III or IV. Supercomplexes I1III2IV2-3 exhibit robust complex III immunoreactivity and activities of complexes I and IV in D2, but with little detected in B6 for I1III2IV2, and I1III2IV3 is not detected in B6. I1III2IV1 and I1III2 are abundant and catalytically active in both strains, but significantly more so in B6. Furthermore, while supercomplex III2IV1 is abundant in D2, none is detected in B6. In aggregate, these results indicate a shift toward more highly assembled supercomplexes in D2. Respiratory supercomplexes are thought to increase electron flow efficiency and individual complex stability, and to reduce electron leak and generation of reactive oxygen species. Our results provide a framework to begin assessing the role of respiratory complex suprastructure in genetic vulnerability and treatment for a wide variety of mitochondrial-related disorders.

Original languageEnglish (US)
Pages (from-to)135-143
Number of pages9
JournalGenes, Brain and Behavior
Volume13
Issue number2
DOIs
StatePublished - Feb 1 2014

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Keywords

  • Brain
  • C57BL/6J
  • Complex I (NADH dehydrogenase)
  • Complex III (cytochrome c reductase/cytochrome bc complex)
  • Complex IV (cytochrome c oxidase)
  • DBA/2J
  • Genetic
  • Mitochondrial supercomplexes
  • Mouse
  • Respiratory chain

ASJC Scopus subject areas

  • Genetics
  • Neurology
  • Behavioral Neuroscience

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