Role of S-palmitoylation in digestive system diseases

Abstract Digestive system diseases, including liver diseases, gastrointestinal cancers, and inflammatory bowel diseases, pose major health challenges worldwide. These conditions are influenced by a range of key metabolic signaling pathways, many of which are regulated by palmitoylation. Palmitoylati...

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Bibliographic Details
Main Authors: Hanqing Li, Qiuxiang Yuan, Shuangshuang Wang, Tao Yu, Xingsi Qi
Format: Article
Language:English
Published: Nature Publishing Group 2025-07-01
Series:Cell Death Discovery
Online Access:https://doi.org/10.1038/s41420-025-02629-z
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Summary:Abstract Digestive system diseases, including liver diseases, gastrointestinal cancers, and inflammatory bowel diseases, pose major health challenges worldwide. These conditions are influenced by a range of key metabolic signaling pathways, many of which are regulated by palmitoylation. Palmitoylation is a type of lipid modification catalyzed by DHHC palmitoyl S-acyltransferases (DHHC-PTAs) and depalmitoylases, which play critical roles in modulating protein localization, stability, and signal transduction. Dysregulation of S-palmitoylation is closely associated with numerous diseases, including these of the digestive system, through multiple key processes such as immune responses, lipid metabolism, and cellular signaling. Decades of investigations have driven the development of a large body of inhibitors targeting zDHHCs and depalmitoylases, such as S-(2-acetamidoethyl) 2-bromohexadecanethioate (MY-D-4), Artemisinin and Lomitapide. This review provides a comprehensive summary of the role of palmitoylation in digestive system diseases, discusses its effect on disease mechanisms. By elucidating the regulatory functions of palmitoylation under these conditions, this review aimed to identify new strategies for the diagnosis and treatment of digestive system disorders.
ISSN:2058-7716