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Mitochondrial Mutations in Cardiac Disorders

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Mitochondrial Dynamics in Cardiovascular Medicine

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

Abstract

Mitochondria individually encapsulate their own genome, unlike other cellular organelles. Mitochondrial DNA (mtDNA) is a circular, double-stranded, 16,569-base paired DNA containing 37 genes: 13 proteins of the mitochondrial respiratory chain, two ribosomal RNAs (rRNAs; 12S and 16S), and 22 transfer RNAs (tRNAs). The mtDNA is more vulnerable to oxidative modifications compared to nuclear DNA because of its proximity to ROS-producing sites, limited presence of DNA damage repair systems, and continuous replication in the cell. mtDNA mutations can be inherited or sporadic. Simple mtDNA mutations are point mutations, which are frequently found in mitochondrial tRNA loci, causing mischarging of mitochondrial tRNAs or deletion, duplication, or reduction in mtDNA content. Because mtDNA has multiple copies and a specific replication mechanism in cells or tissues, it can be heterogenous, resulting in characteristic phenotypic presentations such as heteroplasmy, genetic drift, and threshold effects. Recent studies have increased the understanding of basic mitochondrial genetics, providing an insight into the correlations between mitochondrial mutations and cardiac manifestations including hypertrophic or dilated cardiomyopathy, arrhythmia, autonomic nervous system dysfunction, heart failure, or sudden cardiac death with a syndromic or non-syndromic phenotype. Clinical manifestations of mitochondrial mutations, which result from structural defects, functional impairment, or both, are increasingly detected but are not clear because of the complex interplay between the mitochondrial and nuclear genomes, even in homoplasmic mitochondrial populations. Additionally, various factors such as individual susceptibility, nutritional state, and exposure to chemicals can influence phenotypic presentation, even for the same mtDNA mutation.

In this chapter, we summarize our current understanding of mtDNA mutations and their role in cardiac involvement. In addition, epigenetic modifications of mtDNA are briefly discussed for future elucidation of their critical role in cardiac involvement. Finally, current strategies for dealing with mitochondrial mutations in cardiac disorders are briefly stated.

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Acknowledgements

We apologize for the vast number of outstanding publications that could not be cited because of space limitations. This work was supported by the Priority Research Centers Program (2010-0020224) and the Basic Science Research Program (2015R1A2A1A13001900 and 2015R1D1A3A01015596) through the National Research Foundation of Korea (NRF), funded by the Ministry of Education, Science, and Technology.

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  1. Department of Integrated Biomedical Science, Cardiovascular and Metabolic Disease Center, College of Medicine, Inje University, Busan, 47392, South Korea

    Sung Ryul Lee

  2. National Research Laboratory for Mitochondrial Signaling, Cardiovascular and Metabolic Disease Center, Department of Physiology, College of Medicine, Inje University, Busan, 47392, South Korea

    Jin Han

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

    Gaetano Santulli

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Lee, S.R., Han, J. (2017). Mitochondrial Mutations in Cardiac Disorders. 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_5

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