Xu S, Lu GR. Potential of lysine succinylation as a therapeutic target for gallstone formation: An insightful strategy. World J Gastroenterol 2026; 32(1): 114865 [DOI: 10.3748/wjg.v32.i1.114865]
Corresponding Author of This Article
Guang-Rong Lu, MD, Department of Gastroenterology, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, No. 1111 Wenzhou Avenue, Wenzhou 325000, Zhejiang Province, China. 210257@wzhealth.com
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Gastroenterology & Hepatology
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Letter to the Editor
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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/
Jan 7, 2026 (publication date) through Jan 12, 2026
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World Journal of Gastroenterology
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1007-9327
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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA
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Xu S, Lu GR. Potential of lysine succinylation as a therapeutic target for gallstone formation: An insightful strategy. World J Gastroenterol 2026; 32(1): 114865 [DOI: 10.3748/wjg.v32.i1.114865]
World J Gastroenterol. Jan 7, 2026; 32(1): 114865 Published online Jan 7, 2026. doi: 10.3748/wjg.v32.i1.114865
Potential of lysine succinylation as a therapeutic target for gallstone formation: An insightful strategy
Sheng Xu, Guang-Rong Lu
Sheng Xu, Guang-Rong Lu, Department of Gastroenterology, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, China
Author contributions: Xu S contributed to manuscript writing and editing; Lu GR contributed to conceptualization and critical revisions; all authors have read and approved the final manuscript.
Supported by Wenzhou Science and Technology Bureau, No. Y20240207.
Conflict-of-interest statement: All authors declare that they have no conflict 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: Guang-Rong Lu, MD, Department of Gastroenterology, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, No. 1111 Wenzhou Avenue, Wenzhou 325000, Zhejiang Province, China. 210257@wzhealth.com
Received: October 9, 2025 Revised: November 2, 2025 Accepted: November 13, 2025 Published online: January 7, 2026 Processing time: 97 Days and 12.8 Hours
Abstract
Cholelithiasis has a complex pathogenesis, necessitating better therapeutic and preventive strategies. We recently read with interest Wang et al’s study on lysine acetyltransferase 2A (KAT2A)-mediated adenosine monophosphate-activated protein kinase (AMPK) succinylation in cholelithiasis. Using mouse models and gallbladder mucosal epithelial cells, they found that KAT2A inhibits gallstones through AMPK K170 succinylation, thereby activating the AMPK/silent information regulator 1 pathway to reduce inflammation and pyroptosis. This study is the first to connect lysine succinylation with cholelithiasis, offering new insights and identifying succinylation as a potential therapeutic target. Future research should confirm these findings using patient samples, investigate other post-translational modifications, and use structural biology to clarify succinylation-induced conformational changes, thereby bridging basic research to clinical applications.
Core Tip: The mechanisms of cholelithiasis are incompletely understood. The study by Wang et al is the first to demonstrate that lysine acetyltransferase 2A-mediated succinylation of adenosine monophosphate-activated protein kinase (AMPK) inhibits gallstone formation by activating the AMPK/silent information regulator 1 pathway and suppressing inflammation and pyroptosis in gallbladder mucosal epithelial cells. This finding provides a novel therapeutic target, filling a gap in succinylation research in cholelithiasis. After obtaining meaningful conclusions from basic research, more work is needed, specifically horizontal and vertical research expansions and verification using real-world patient specimens, to bridge the gap from basic research to clinical practice.
