Role of mitochondrial APE1 in early stages of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the leading cause of primary liver cancers. Surveillance of individuals at specific risk of developing HCC, early diagnostic markers, and new therapeutic approaches are essential to obtain a reduction in disease-related mortality. Apurinic/apyrimidinic endonuclease 1 (APE1) expression levels and its cytoplasmic localization have been reported to correlate with a lower degree of differentiation and shorter survival rate. The aim of this thesis is to fully investigate the role of the mitochondrial form of APE1 in HCC. To better evaluate the effect of a delocalization of APE1 from the nucleus to mitochondria, analysis of the translocation of the endonuclease from the intermembrane space to the matrix has been performed, with a deep sight on the innermembrane translocator involved in the process. Finally, a view on possible therapeutic approaches aimed to block APE1 translocation inside mitochondria has been proposed, reporting preliminary experiments based on a peptide targeting the MIA pathway, the main responsible for APE1 transport inside mitochondria.