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Over time, mutated mtDNA molecules can undergo clonal expansion, and once the mutational burden exceeds a critical thresholdtypically 60% and 90% they produce a biochemical defect in OXPHOS, a concept referred to as the mtDNA mutational load (112)

Animal Models Wistar rats from our breeding colonies (Faculty of Medicine, University of Coimbra, and NOVA Medical School) were kept under standard conditions [25,26]