title: Cardiac mitochondria in heart failure: decrease in respirasomes and oxidative phosphorylation.
abstract: OBJECTIVE
  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.
  
  
  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.
authors: Department of Medicine, School of Medicine, Case Western Reserve University, 10900 Euclid Avenue, Cleveland 44106-4981, OH, USA.
authors: Mariana G
authors: MG
authors: Rosca
authors: Edwin J
authors: EJ
authors: Vazquez
authors: Janos
authors: J
authors: Kerner
authors: William
authors: W
authors: Parland
authors: Margaret P
authors: MP
authors: Chandler
authors: William
authors: W
authors: Stanley
authors: Hani N
authors: HN
authors: Sabbah
authors: Charles L
authors: CL
authors: Hoppel
mesh_terms: D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000818:Animals; D019069:Cell Respiration; D004285:Dogs; D004579:Electron Transport; D045222:Electron Transport Chain Complex Proteins / Q000378:metabolism*; D006333:Heart Failure / Q000378:metabolism*; D006439:Hemodynamics; D026901:Membrane Transport Proteins / Q000378:metabolism; D008929:Mitochondria, Heart / Q000378:metabolism*; D017240:Mitochondrial Myopathies / Q000378:metabolism; D010085:Oxidative Phosphorylation; D010088:Oxidoreductases / Q000378:metabolism
chemical_list: D045222:Electron Transport Chain Complex Proteins; D026901:Membrane Transport Proteins; D000255:Adenosine Triphosphate; D010088:Oxidoreductases