Impaired mitochondrial respiratory chain and bioenergetics during chagasic cardiomyopathy development

Galina Vyatkina, Vandanajay Bhatia, Arpad Gerstner, John Papaconstantinou, Nisha Garg

Research output: Contribution to journalArticle

52 Scopus citations

Abstract

In this study, we evaluated the activities of respiratory chain complexes and oxidative phosphorylation (OXPHOS) capacity of the heart to gain insights into the pathological significance of mitochondrial dysfunction in chagasic cardiomyopathy (CCM). In a murine model of Trypanosoma cruzi infection, biochemical and histochemical analysis of the cardiac mitochondria revealed deficiency of the respiratory chain complexes (CI-CV) in infected mice; the inhibition of CI activity was more pronounced in the acute infection phase, CIII was constitutively repressed throughout the infection and disease phase, and the CV defects appeared in chronic phase only. A substantial decline in cardiac mtDNA content (54-60%) and mitochondria-encoded transcripts (50-65%) with disease development indicated that the alterations in mtDNA contribute to the quantitative deficiencies in respiratory chain activity in chagasic hearts. The observations of a selective inhibition of redox-sensitive CI and CIII complexes that are also the site of free radical generation in mitochondria, and the decline in cardiac mtDNA content in infected mice, all support the free radical hypothesis of mitochondria dysfunction in CCM. Consequently, OXPHOS-mediated ATP synthesis capacity of the cardiac mitochondria in infected mice was substantially reduced (37-50%), suggesting an energy homeostasis in the affected tissue.

Original languageEnglish (US)
Pages (from-to)162-173
Number of pages12
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Volume1689
Issue number2
DOIs
StatePublished - Jun 28 2004

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Keywords

  • BN-PAGE
  • CCM
  • CI
  • CII
  • Chagasic cardiomyopathy
  • Free radical
  • NADH-ubiquinone oxidoreductase
  • Oxidative phosphorylation
  • Respiratory chain complex
  • Trypanosoma cruzi
  • blue native-polyacrylamide gel electrophoresis
  • chronic chagasic myocardiopathy
  • mtDNA content

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology

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