The aim of this study was to examine the potential role of Sirt3 in the regulation of NEIL1, NEIL2, MUTYH, APE1, and LIG3 mitochondrial proteins by assessing their physical interactions, influence on activity, cooperation in oxidative damage removal, and finally role in apoptosis process in colorectal cancer (CRC) cells. The gene discussed is SIRT3; the disease is colorectal cancer.