The Correlation Between Mfn2 And P53 In The Inhibition Of Hepatocellular Carcinoma Cell Proliferation

Mitochondrial GTPase mitofusin-2 (Mfn2), also called hyperplasia suppressor gene (HSG), was firstly characterized by Chen et al. as a cell proliferation suppressor. It was shown that the Mfn2 has potential apoptotic effects, which may be mediated by the mitochondrial apoptosis pathway. Further research indicated that Mfn2 was involved in mitochondrial fusion and contributed to the maintenance and operation of the mitochondrial network. P53 serves as a gatekeeper of the genome, by integrating various signals into different biological processes, such as apoptosis, cell cycle arrest, senescence, differentiation and antiangiogenesis. Previous studies have shown that most of these functions are mediated by the ability of p53 as a transcriptional activator through regulation of its downstream target genes. Bioinformatics analysis reveals a p53-binding site in the Mfn2 promoter region. We found that p53 protein binds the Mfn2 promoter directly in vitro and in vivo. In addition, Mfn2 mRNA and protein levels can be up-regulated in a p53-dependent manner. Furthermore, luciferase assays showed that the Mfn2 promoter activity was elevated by the p53, but not the promoter in mutant form. Our results indicate that Mfn2 is a novel p53-inducible target that may contribute insights in the function of Mfn2, particularly its ability to inhibit proliferation, promote apoptosis and to exert tumor-repressive effects.