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

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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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Electron Transport
Cardiomyopathies
Energy Metabolism
Mitochondria
Mitochondrial DNA
Oxidative Phosphorylation
Free Radicals
Infection
Trypanosoma cruzi
Oxidation-Reduction
Homeostasis
Adenosine Triphosphate

Keywords

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

ASJC Scopus subject areas

  • Molecular Biology
  • Molecular Medicine
  • Biophysics

Cite this

Impaired mitochondrial respiratory chain and bioenergetics during chagasic cardiomyopathy development. / Vyatkina, Galina; Bhatia, Vandanajay; Gerstner, Arpad; Papaconstantinou, John; Garg, Nisha.

In: Biochimica et Biophysica Acta - Molecular Basis of Disease, Vol. 1689, No. 2, 28.06.2004, p. 162-173.

Research output: Contribution to journalArticle

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