LETTER TO THE EDITOR
Mitochondrial dysfunction in heart failure
Jose Marin-Garcia, MD
The Molecular Cardiology and Neuromuscular Institute, 75 Raritan Avenue, Highland Park, New Jersey 08904, USA
tmci{at}att.net
I read with interest the report in the Journal by Scheubel et al. (1). Although their conclusion that a deficit in the activity of respiratory chain complex I may not be due to generalized damage of mitochondrial deoxyribonucleic acid (DNA) and gene expression is most likely true, their statement in the discussion that "in an experimental model of tachypacing-induced heart failure without any drug treatment, a depression in the activities of all complexes containing mitochondrially encoded subunits, including the mitochondrial adenosine triphosphatase, was described ..., indicating disturbed mitochondrial gene expression," is inaccurate.
Marin-Garcia et al. (2) in their study of mitochondrial function in pacing-induced cardiac failure reported that the activity levels of complexes I and IV (complexes containing mitochondrially encoded subunits) were unchanged (normal) relative to controls. Only one complex of the electron transport chain (complex III) and adenosine triphosphate synthase (complex V) were affected without changes in peptide content of specific mitochondrial proteins. The reduced levels of complex III and complex V activities did not appear to be due to generalized mitochondrial damage, necrosis, or overall decreased levels of mitochondria as gauged by unchanged levels of respiratory complex I, complex II (nuclear encoded), complex IV, and citrate synthase (also nuclear encoded). The levels of mitochondrial DNA deletions (7.4 kb) were extremely low in comparison to wild-type genomes and probably of no significance. Therefore, the investigators’ conclusion that depression in the activity levels of the respiratory enzymes and complex V in the pacing-induced cardiac failure indicate disturbed mitochondrial gene expression is misguided. However, I do agree that the protective role of drug treatment against mitochondrial DNA damage remains to be proven.
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References
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1. Scheubel RJ, Tostlebe M, Sim A, et al. Dysfunction of mitochondrial respiratory chain complex I in human failing myocardium is not due to disturbed mitochondrial gene expression. J Am Coll Cardiol. 2002;40:2174–2181[Abstract/Free Full Text]
2. Marin-Garcia J, Goldenthal MJ, Moe GW. Abnormal cardiac and skeletal muscle mitochondrial function in pacing-induced cardiac failure. Cardiovasc Res. 2001;52:103–110[CrossRef][Medline]
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