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

Administration of the fatty acid analogue tetradecylthioacetic acid (TTA) t o rodents up-regulates peroxisomal and mitochondrial lipid-metabolizing enz ymes and induces a proliferation of these organelles in hepatocytes. We sho w 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 th e liver mtDNA followed by a 1.6-fold increase in the content of mtDNA. In a ddition, a transient three-fold increase in the mitochondrial thymidine kin ase (TK2) activity and a slight increase in the DNA polymerase gamma activi ty was observed, indicating that the TTA induced mitochondrial proliferatio n is linked to an up-regulation of the mitochondrial thymidine kinase activ ity.