Potential of lysine succinylation as a therapeutic target for gallstone formation: An insightful strategy

Cholelithiasis has a complex pathogenesis, necessitating better therapeutic and preventive strategies. We recently read with interest Wang <i>et al</i>'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.