Our recently published work shows that anti-cancer drug bortezomib can block the TFAM degradation and increase mtDNA copy numbers in cells with extremely low mtDNA by inhibiting Lon protease activity [22].In human oral cancer cell OEC-M1 and FADU, over-expression of Lon protease resulted in the enhancing of mitochondrial ROS generation, which is related to Lon-mediated up-regulation of a mitochondrial Fe-S protein in complex I of electron transport chain (NDUFS8) [28]. Here, TFAM is linked to lip and oral cavity carcinoma.