Indeed, studies in mice and rabbits demonstrated that chronic anthracycline-induced heart failure correlates with imbalances in mitochondrial mass and reduced expression of genes regulating mitochondrial homeostasis.62, 63 However, whether TOP2-dependent DSBs in mtDNA or TOP2-independent oxidative mtDNA base lesions cause depletion of mtDNA content is hard to discriminate. This evidence concerns the gene TOP2A and heart failure.