Taken together, these results provided p-Drp1Ser616-based evidence linking a novel PINK1-mediated p-Drp1Ser616 activation mechanism for the regulation of mito-COX-2 to the PINK1/p-Drp1Ser616 interaction and its co-localization in endogenous mitochondrial protein machinery, which further modulated the mitochondrial fission in HCC cells. The gene discussed is PINK1; the disease is hepatocellular carcinoma.