mtDNA damage in the development of heart failure

CONTINUOUS ATP GENERATION is obligatory to support the massive energetic demand of contractility (20). Oxidative phosphory-lation (OXPHOS) mediated by electron transport across the inner mitochondrial membrane accounts for more than 90 % of the ATP synthesized in cardiomyocytes (6). Each cardiomyo-cyte has thousands of mitochondria, and each mitochondrion contains its own DNA (22). Mitochondrial DNA (mtDNA) is a double-stranded circular genome comprised of 16,600 base pairs that encodes 13 proteins of the electron transport chain (ETC), 2 ribosomal RNAs, and 22 transfer RNAs (22). Al-though mtDNA only encodes a small portion of ETC complex subunits, most ETC proteins are encoded by nuclear DNA, perturbations in mtDNA are associated with the pathogenesis of numerous diseases defined by impaired energy production (22). It is not surprising that the manifestations of mitochon