Alterations of the mitochondrial respiratory chain in human dilated cardiomyopathy.
The defects underlying the impairment of systolic pump function in human dilated cardiomyopathy (DCM) are not known. We isolated mitochondrial particles from 10 hearts of transplant recipients with DCM and from nine normal hearts not used for transplantation. Yield was similar in both groups (2.77 vs 2.81 mg mitochondrial protein per gram heart). Cytochrome content (difference spectrophotometry) was found reduced in DCM mitochondria, e.g. cytochrome c was 0.295 +/- 0.06 in the DCM group and 0.371 +/- 0.04 mumol g-1 in the control group (P less than 0.05). Enzymatic activity of the cytochrome-containing complexes III (3.77 +/- 0.82 vs 4.95 +/- 1.15 mumol min-1.mg-1) and IV (2.63 +/- 0.96 vs 3.65 +/- 0.6 mumol min-1.mg-1) of the respiratory chain was reduced in the DCM group (P less than 0.05). Complex IV, the cytochrome c oxidase, in the DCM group showed impaired activity also in whole heart homogenates (0.173 +/- 0.04 vs 0.258 +/- 0.8 mumol min-1.mg-1). Subunit composition of the cytochrome c oxidase on sodium dodecyl sulphate-gel electrophoresis did not differ between DCM and normal hearts. Activity of complexes II and V of the respiratory chain, not containing cytochromes, was unchanged in DCM mitochondria compared with the control group. The present data show a decrease in cytochrome content and in cytochrome-dependent enzyme activity in human dilated cardiomyopathy. Further studies are necessary to clarify whether these findings are specific for dilated cardiomyopathy or whether they are epiphenomena of failing hearts.
Buchwald
A
A
Department of Cardiology, University of Göttingen, F.R.G.
Till
H
H
Unterberg
C
C
Oberschmidt
R
R
Figulla
H R
HR
Wiegand
V
V
D001081:Apyrase / Q000378:metabolism; D002311:Cardiomyopathy, Dilated / Q000201:enzymology*; D003580:Cytochromes / Q000032:analysis; D004579:Electron Transport / Q000502:physiology; D042963:Electron Transport Complex II; D014450:Electron Transport Complex III / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000378:metabolism; D006801:Humans; D008929:Mitochondria, Heart / Q000201:enzymology*; D009097:Multienzyme Complexes / Q000378:metabolism; D010088:Oxidoreductases / Q000378:metabolism; D013385:Succinate Dehydrogenase / Q000378:metabolism
D003580:Cytochromes; D009097:Multienzyme Complexes; D010088:Oxidoreductases; D042963:Electron Transport Complex II; D013385:Succinate Dehydrogenase; D003576:Electron Transport Complex IV; D001081:Apyrase; D014450:Electron Transport Complex III