The heart in neuromuscular disease: primary mitochondrial diseases
Mitochondria are responsible for energy production in most eukaryotic cells. Each cell contains at least one mitochondrion and every mitochondrion contains two to ten copies of a circular DNA molecule (mitochondrial DNA or mtDNA). Cardiomyocytes contain approximately 10,000 mtDNA copies. MtDNA is composed of around 16,500 base pairs and 37 genes encoding 13 subunits of the respiratory chain complexes I, III, IV, and V, 22 mitochondrial tRNAs and 2 rRNAs. With each cell division, mitochondria and mtDNA are randomly distributed to daughter cells. In humans, mitochondria are inherited exclusively from the mother. In healthy people mtDNA copies are usually identical at birth (homoplasmy) but with ageing, mtDNA is particularly prone to somatic mutation because, unlike nuclear DNA, it is continuously replicated, even in non-dividing tissues such as myocardium. This can lead to the propagation of somatic mutations within single cells by a process called clonal expansion. In addition, mtDNA lacks an extensive DNA repair mechanism.