In this study, we report that a mitochondrial protein Sirt3, despite improving the mitochondrial function, induces DNA damage and tumor-suppressive factors, affects p53 by disruption of the ERα–p53 interaction, reduces response of the MCF-7 cells to E2 treatment, and consequently inhibits the migration and clonogenic capacity of the cells. The gene discussed is SIRT3; the disease is neoplasm.