© 2001 by European Society of Cardiology
Copyright © 2000, European Society of Cardiology
Mitochondrial pathology in cardiac failure
aThe Molecular Cardiology Institute, 75 Raritan Ave., Highland Park, NJ 08904, USA
bDepartment of Medicine, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada
* Corresponding author. Tel.: +1-732-220-1719; fax: +1-732-220-2992 tmci@worldnet.att.net
Received 12 May 2000; accepted 26 September 2000
KEYWORDS Energy metabolism; Heart failure; Mitochondria; Oxidative phosphorylation
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1 Introduction |
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The heart is highly dependent for its function on oxidative energy generated in mitochondria, primarily by fatty acid β-oxidation, respiratory electron chain and oxidative phosphorylation (OXPHOS). In this review, we survey the available evidence that mitochondrial dysfunction may play a pivotal role in cardiac failure. We also discuss how mitochondrial dysfunction may be related to other critical cellular and molecular changes found in cardiac hypertrophy and failure, including dysfunctional structural and cytoskeletal proteins, apoptosis, calcium flux and handling, and signalling pathways. The review also focuses on the biochemical and molecular changes in severe heart failure secondary to primary cardiomyopathy (dilated/hypertrophic) in humans as well as findings in animal models of heart failure related to volume and/or pressure overload.
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2 Mitochondria are the major source of bioenergy in the cell |
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Mitochondria are abundant in energy-demanding cardiac tissue constituting 20–40% of cellular volume (greater proportion than in skeletal muscle). Mitochondrial energy production depends on genetic factors which modulate normal mitochondrial function including enzyme
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3 What is the evidence for myocardial dependency on mitochondrial function? |
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3.1 Mitochondrial dysfunction and cardiomyopathy: support from human studies
3.2 Nuclear mutations in mitochondrial components
3.3 Support from animal models
3.4 Other cellular/molecular events in cardiac failure
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4 To what extent do cellular and molecular changes associated with mitochondria contribute to cardiac failure? |
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4.1 Mitochondrial function and cardiac hypertrophy
4.2 Mitochondrial function and structural/cytoskeletal protein defects
4.3 Calcium signalling and mitochondrial function in cardiac failure
4.4 Mitochondrial function and apoptosis in cardiac failure
4.5 Other mitochondrial enzymes in cardiac failure
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5 What events occurring in cardiac failure are truly tissue-specific? |
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6 Future prospects |
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