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 monophos...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 posttranslational modifications,and use structural biology to clarify succinylationinduced conformational changes,thereby bridging basic research to clinical applications.展开更多
基金Supported by Wenzhou Science and Technology Bureau,No.Y20240207.
文摘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 posttranslational modifications,and use structural biology to clarify succinylationinduced conformational changes,thereby bridging basic research to clinical applications.