Protein succinylation, hepatic metabolism, and liver diseases

Figure 3 Succinylation affects the progression of fatty liver, hepatitis, and hepatocellular carcinoma. A: P50 stabilizes histone deacetylase 1 protein to keep desuccinylation of sterol-regulatory element binding protein 1c, thereby promoting fatty liver. Sirtuin 7 (SIRT7)-mediated desuccinylation of SIRT7 mediates the desuccinylation of arginine methyltransferase 5 at K387 promotes fatty liver by inducing arginine methylation of SREBP1a; B: IFN-α inhibits lysine acetyltransferase 2A-mediated succinylation of histone H3K79 and SIRT7 promotes desuccinylation of histone H3K122, which restrains viral replication and hepatitis; C: Sirtuin 5 deficiency activates acyl-CoA oxidase 2 succinylation, leading to elevated bile acid levels and promoting hepatocellular carcinoma (HCC). Histone acetyltransferase 1 not only promotes hepatocellular carcinogenesis by activating H3K122 succinylation but also promotes the glycolytic pathway by promoting succinylation of phosphoglycerate mutase 1 at K99, thereby promoting HCC. HBV: Hepatitis B virus; PRMT5: SIRT7 mediates the desuccinylation of arginine methyltransferase 5; SREBP: Sterol-regulatory element binding protein; ACOX2: Acyl-CoA oxidase 2; HAT1: Histone acetyltransferase 1; HCC: Hepatocellular carcinoma; PGAM1: Phosphoglycerate mutase 1.