Cardiac mitochondria in heart failure: Decrease in respirasomes and oxidative phosphorylation

Mariana G. Rosca, Edwin J. Vazquez, Janos Kerner, William Parland, Margaret P. Chandler, William Stanley, Hani N. Sabbah, Charles L. Hoppel

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291 Scopus citations


Aims: Mitochondrial dysfunction is a major factor in heart failure (HF). A pronounced variability of mitochondrial electron transport chain (ETC) defects is reported to occur in severe acquired cardiomyopathies without a consistent trend for depressed activity or expression. The aim of this study was to define the defect in the integrative function of cardiac mitochondria in coronary microembolization-induced HF. Methods and results: Studies were performed in the canine coronary microembolization-induced HF model of moderate severity. Oxidative phosphorylation was assessed as the integrative function of mitochondria, using a comprehensive variety of substrates in order to investigate mitochondrial membrane transport, dehydrogenase activity and electron-transport coupled to ATP synthesis. The supramolecular organization of the mitochondrial ETC also was investigated by native gel electrophoresis. We found a dramatic decrease in ADP-stimulated respiration that was not relieved by an uncoupler. Moreover, the ADP/O ratio was normal, indicating no defect in the phosphorylation apparatus. The data point to a defect in oxidative phosphorylation within the ETC. However, the individual activities of ETC complexes were normal. The amount of the supercomplex consisting of complex I/complex III dimer/complex IV, the major form of respirasome considered essential for oxidative phosphorylation, was decreased. Conclusions: We propose that the mitochondrial defect lies in the supermolecular assembly rather than in the individual components of the ETC.

Original languageEnglish
Pages (from-to)30-39
Number of pages10
JournalCardiovascular Research
Issue number1
StatePublished - Oct 2008


  • Electron transport chain complexes
  • Heart failure
  • Mitochondria
  • Oxidative phosphorylation
  • Respirasomes


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