Succinylation: novel molecular mechanisms and prospects for targeted therapy in liver diseases

Succinylation is a novel post-translational modification involving the attachment of a negatively charged succinyl group to lysine residues, which fundamentally alters the structure and function of substrate proteins. The liver, the metabolic center of the body, is a critical target for succinylation because of its high metabolic activity. Growing evidence suggests that succinylation is a core pathological mechanism that bridges hepatic metabolic dysfunction and disease progression by modulating metabolic enzyme activity, influencing epigenetic status, and remodeling the immune microenvironment. This review aimed to systematically outline the molecular features and regulatory networks of succinylation, dissect its mechanistic roles in major liver diseases, and synthesize current therapeutic strategies, including clinical drug repurposing, small-molecule agents, and traditional Chinese medicinal compounds that target this modification. Collectively, these insights offer a novel theoretical framework and promising therapeutic direction for the management of liver diseases.