Abstract
Mitochondria play a key role in the normal functioning of the heart, and in the pathogenesis and development of various types of heart disease. Physiologically, mitochondrial ATP supply needs to be matched to the often sudden changes in ATP demand of the heart, and this is mediated to a large extent by the mitochondrial Ca2+ transport pathways allowing elevation of mitochondrial [Ca2+] ([Ca2+]m). In turn this activates dehydrogenase enzymes to increase NADH and hence ATP supply. Pathologically, [Ca2+]m is also important in generation of reactive oxygen species, and in opening of the mitochondrial permeability transition pore (MPTP); factors involved in both ischaemia-reperfusion injury and in heart failure. The MPTP has proved a promising target for protective strategies, with inhibitors widely used to show cardioprotection in experimental, and very recently human, studies. Similarly mitochondrially-targeted antioxidants have proved protective in various animal models of disease and await clinical trials. The mitochondrial Ca2+ transport pathways, although in theory promising therapeutic targets, cannot yet be targeted in human studies due to non-specific effects of drugs used experimentally to inhibit them. Finally, specific mitochondrial cardiomyopathies due to mutations in mtDNA have been identified, usually in a gene for a tRNA, which, although rare, are almost always very severe once the mutation has exceeded its threshold.
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Abbreviations
- mCU:
-
Mitochondrial calcium uniporter
- mNCX:
-
Mitochondrial sodium calcium exchanger
- MPTP:
-
Mitochondrial permeability transition pore
- ROS:
-
Reactive oxygen species
- RuR:
-
Ruthenium red
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Griffiths, E.J. (2012). Mitochondria and Heart Disease. In: Scatena, R., Bottoni, P., Giardina, B. (eds) Advances in Mitochondrial Medicine. Advances in Experimental Medicine and Biology, vol 942. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-2869-1_11
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DOI: https://doi.org/10.1007/978-94-007-2869-1_11
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