Liu S, Li R, Sun YW, Lin H, Li HF. Protein succinylation, hepatic metabolism, and liver diseases. World J Hepatol 2024; 16(3): 344-352 [PMID: 38577527 DOI: 10.4254/wjh.v16.i3.344]
Corresponding Author of This Article
Hai-Fang Li, Doctor, Associate Professor, College of Life Sciences, Shandong Agricultural University, No. 61 Daizong Street, Tai’an 271018, Shandong Province, China. haifangli@sdau.edu.cn
Research Domain of This Article
Cell Biology
Article-Type of This Article
Minireviews
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Hepatol. Mar 27, 2024; 16(3): 344-352 Published online Mar 27, 2024. doi: 10.4254/wjh.v16.i3.344
Protein succinylation, hepatic metabolism, and liver diseases
Shuang Liu, Rui Li, Ya-Wen Sun, Hai Lin, Hai-Fang Li
Shuang Liu, Hai Lin, College of Animal Science and Veterinary Medicine, Shandong Agricultural University, Tai’an 271018, Shandong Province, China
Rui Li, Ya-Wen Sun, Hai-Fang Li, College of Life Sciences, Shandong Agricultural University, Tai’an 271018, Shandong Province, China
Co-first authors: Shuang Liu and Rui Li.
Author contributions: Liu S and Li R wrote the original draft, created the figures, and revised the manuscript; Sun YW wrote the original draft and created the figures; Lin H supervised and verified the paper; Li HF supervised, conceived, verified, reviewed, and edited the manuscript; All authors were involved in the critical review of the results and have contributed to reading and approving the final manuscript. Liu S and Li R contributed equally to this work as co-first authors. The reasons for designating Liu S and Li R as co-first authors are twofold. First, the review was prepared as a collaborative effort with Liu S and Li R contributing equally to literature searching, draft writing, figure drawing, and manuscript revising. The designation of co-first authors authorship reflects the distribution of responsibilities and burdens associated with the time and effort required to complete the review and ensure effective communication and management of post-submission matters. Second, Liu S and Li R are skilled in different fields, which promotes the most comprehensive and in-depth discussion of the review topic, ultimately enriching reader understanding by offering various expert perspectives.
Conflict-of-interest statement: The authors declare that they have no conflicts of interest.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Hai-Fang Li, Doctor, Associate Professor, College of Life Sciences, Shandong Agricultural University, No. 61 Daizong Street, Tai’an 271018, Shandong Province, China. haifangli@sdau.edu.cn
Received: December 11, 2023 Peer-review started: December 11, 2023 First decision: December 29, 2023 Revised: January 8, 2024 Accepted: March 1, 2024 Article in press: March 1, 2024 Published online: March 27, 2024
Abstract
Succinylation is a highly conserved post-translational modification that is processed via enzymatic and non-enzymatic mechanisms. Succinylation exhibits strong effects on protein stability, enzyme activity, and transcriptional regulation. Protein succinylation is extensively present in the liver, and increasing evidence has demonstrated that succinylation is closely related to hepatic metabolism. For instance, histone acetyltransferase 1 promotes liver glycolysis, and the sirtuin 5-induced desuccinylation is involved in the regulation of the hepatic urea cycle and lipid metabolism. Therefore, the effects of succinylation on hepatic glucose, amino acid, and lipid metabolism under the action of various enzymes will be discussed in this work. In addition, how succinylases regulate the progression of different liver diseases will be reviewed, including the desuccinylation activity of sirtuin 7, which is closely associated with fatty liver disease and hepatitis, and the actions of lysine acetyltransferase 2A and histone acetyltransferase 1 that act as succinyltransferases to regulate the succinylation of target genes that influence the development of hepatocellular carcinoma. In view of the diversity and significance of protein succinylation, targeting the succinylation pathway may serve as an attractive direction for the treatment of liver diseases.
Core Tip: Succinylation is the process of transferring succinyl groups through enzymatic and non-enzymatic means using succinyl CoA as a direct substrate. The succinylation degree could be promoted by succinyltransferases (e.g., lysine acetyltransferase 2A, histone acetyltransferase 1, α-ketoglutarate dehydrogenase complex, and carnitine palmitoyltransferase 1A). Desuccinylases including CobB, sirtuin 5, and sirtuin 7 negatively regulate protein succinylation. Several proteins and enzymes in glucose, amino acid, and lipid metabolisms are succinylated in the liver. Succinylation is associated with the progression of several liver diseases. Proteins with varied levels of succinylation may be potential targets for the treatment of fatty liver, hepatitis, and hepatocellular carcinoma.
