Transient up-regulation of liver mitochondrial thymidine kinase activity in proliferating mitochondria

Administration of the fatty acid analogue tetradecylthioacetic acid (TTA) to rodents up-regulates peroxisomal and mitochondrial lipid-metabolizing enzymes and induces a proliferation of these organelles in hepatocytes. We show here that male NMRI mice fed a diet containing 0.3% (w/w) TTA revealed a transient two-fold increase in the incorporation of [H-3] thymidine into the liver mtDNA followed by a 1.6-fold increase in the content of mtDNA. In addition, a transient three-fold increase in the mitochondrial thymidine kinase (TK2) activity and a slight increase in the DNA polymerase gamma activity was observed, indicating that the TTA induced mitochondrial proliferation is linked to an up-regulation of the mitochondrial thymidine kinase activity.