• Sung Ryul Lee and Jin Han.
• Department of Integrated Biomedical Science, Cardiovascular and Metabolic Disease Center, College of Medicine, Inje University, Busan, 47392, South Korea.
• Adv Exp Med Biol. 2017 Jan 1; 982: 81-111.

AbstractMitochondria 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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