Alterations of the mitochondrial respiratory chain in human dilated cardiomyopathy
Buchwald, A.; Till, H.; Unterberg, C.; Oberschmidt, R.; Figulla, H.R.; Wiegand, V.
European Heart Journal 11(6): 509-516
1990
ISSN/ISBN: 0195-668X PMID: 2161769 Document Number: 365839
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 trnasplantation. Yield was similar in both groups (2.77 vs 2.81 mg mitochondria 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 .mu.mol g-1 in the control group (P < 0.05). Enzymatic activity of the cytochrome-containing complexes III (3.77 .+-. 0.82 vs 4.95 .+-. 1.15 .mu.mol min-1 .cntdot. mg-1) and IV (2.63 .+-. 0.96 vs 3.65 .+-. 0.6 .mu.mol min-1 .cntdot. mg-1) of the respiratory chain was reduced in the DCM group (P < 0.05). Complex IV, the cytochrome c oxidase, in the DCM group showed impaired activity also in whole heart homnogenates (0.173 .+-. 0.04 vs 0.258 .+-. 0.8 .mu.mol min-1 .cntdot. 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 thesse findings are specific for dilated cardiomyopathy or whether the are epiphenomena of failing hearts.