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Mitochondrial Bioenergetics and Dysfunction in Failing Heart

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Mitochondrial Dynamics in Cardiovascular Medicine

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 982))

Abstract

Energy insufficiency has been recognized as a key feature of systolic heart failure. Although mitochondria have long been known to sustain myocardial work energy supply, the capacity to therapeutically target mitochondrial bioenergetics dysfunction is hampered by a complex interplay of multiple perturbations that progressively compound causing myocardial failure and collapse. Compared to non-failing human donor hearts, activity rates of complexes I and IV, nicotinamide nucleotide transhydrogenase (NADPH-transhydrogenase, Nnt) and the Krebs cycle enzymes isocitrate dehydrogenase, malate dehydrogenase and aconitase are markedly decreased in end-stage heart failure. Diminished REDOX capacity with lower total glutathione and coenzyme Q10 levels are also a feature of chronic left ventricular failure. Decreased enzyme activities in part relate to abundant and highly specific oxidative, nitrosylative, and hyperacetylation modifications. In this brief review we highlight that energy deficiency in end-stage failing human left ventricle predominantly involves concomitantly impaired activities of key electron transport chain and Krebs cycle enzymes rather than altered expression of respective genes or proteins. Augmented oxidative modification of these enzyme subunit structures, and the formation of highly reactive secondary metabolites, implicates dysfunction due to diminished capacity for management of mitochondrial reactive oxygen species, which contribute further to progressive decreases in bioenergetic capacity and contractile function in human heart failure.

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Acknowledgements

The Authors acknowledge research funding supported from the National Health and Medical Research Council of Australia, the National Heart Foundation of Australia, the Royal Children’s Hospital 1000 Foundation, HeartKids Australia and the Victorian Government’s Operational Infrastructure Support Program.

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Authors and Affiliations

  1. Heart Research, Murdoch Children’s Research Institute, Melbourne, Australia

    Freya L. Sheeran & Salvatore Pepe

  2. Department of Paediatrics, University of Melbourne, Melbourne, Australia

    Freya L. Sheeran & Salvatore Pepe

  3. Royal Children’s Hospital, Melbourne, Australia

    Freya L. Sheeran & Salvatore Pepe

  4. Department of Cardiology, Royal Children’s Hospital, 50 Flemington Road, VIC, 3052, Melbourne, Australia

    Salvatore Pepe

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Correspondence to Salvatore Pepe .

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  1. Dept. of Biomedical Advanced Sciences, Federico II University, Naples, Italy

    Gaetano Santulli

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Sheeran, F.L., Pepe, S. (2017). Mitochondrial Bioenergetics and Dysfunction in Failing Heart. In: Santulli, G. (eds) Mitochondrial Dynamics in Cardiovascular Medicine. Advances in Experimental Medicine and Biology, vol 982. Springer, Cham. https://doi.org/10.1007/978-3-319-55330-6_4

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