However, HBx in the mitochondria is also regulated by the ubiquitination system of the outer mitochondrial membrane in the mtUPR; the outer mitochondrial membrane mitochondrial ubiquitin ligase (MARCH5) mediates the degradation of HBx via the ubiquitin proteasome and inhibits ROS generation, stabilizes the quality of mitochondria, reduces inflammation caused by HBx, and inhibits the initiation of HCC. Here, MARCHF5 is linked to hepatocellular carcinoma.