Alterations of the mitochondrial respiratory chain in human dilated cardiomyopathy

Abstract

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.

Cardiac gene expression profile in rats with terminal heart failure and cachexia

“…Mitochondrial function changes during development and is altered in failing human hearts (10,32). We found a decrease in three of seven mitochondrial multicomplex units in THFdTGR with our chip approach (cytochrome B, cytochrome c oxidase, ATP synthase).…”

Mitochondria in the human heart

“…End-stage HF was associated with multiple mitochondrial functional injuries, e.g., a decrease of ETC activities per muscle mass, most notably CI (Scheubel et al 2002), CIII (Buchwald et al 1990;Jarreta et al 2000;Marin-Garcia et al 1995), and CIV (Arbustini et al 1998;Quigley et al 2000), and a decrease in OXPHOS capacity in the presence of substrates directing electrons into CI in permeabilized fibers (Saks et al 1991;Sharov et al 2000). Part of the loss of mitochondrial ETC activity or OXPHOS per g of muscle is explainable by a decrease in mitochondrial content occurring also in endstage HF (Kalsi et al 1999;Nascimben et al 1996;Quigley et al 2000).…”

Mitochondrial fission is required for cardiomyocyte hypertrophy via a Ca2+-calcineurin signalling pathway

“…Furthermore, several studies have shown that mitochondrial disorders often present themselves as cardiomyopathies. For example, mutations that decrease mitochondrial oxidative phosphorylation or alter the activity of proteins involved in the transport of mitochondrial substrates (such as adenine nucleotide and fatty acid transporter proteins), can cause cardiac hypertrophy, as can the depletion of mitochondrial DNA itself (Buchwald et al, 1990;Graham et al, 1997;Stojanovski et al, 2004).…”