Fig. 4

Role of mitochondrial APE1 in HCC tumor progression. In healthy cells, APE1 localization is mainly nuclear. Nevertheless, a physiological amount of the protein is also present in mitochondria (healthy cell). During tumorigenic processes and in low grade tumors, APE1 is overexpressed. Increased expression of its mitochondrial transporter Mia40 determines increased levels of mitochondrial APE1, which determines a higher rate of mtDNA repaired. In high grade tumors, APE1 delocalizes from nuclei to cytoplasm; mitochondria show dysfunction, the protein import is impaired, and less APE1 is detected in the organelle. At this final stage, exosomes containing APE1 have been detected in serum (sAPE1)