Succinylation: A novel regulatory axis in cholelithiasis-insights from lysine acetyltransferase 2A/adenosine monophosphate-activated protein kinase signaling

Abstract

Cholelithiasis represents a common clinical condition within the digestive tract and continues to pose a substantial global health challenge, largely due to its high rate of recurrence and a scarcity of effective non-surgical interventions. Although protein succinylation has been widely characterized as a post-translational modification, its implications in cholelithiasis pathogenesis had remained poorly defined. A groundbreaking study by Wang et al demonstrates that lysine acetyltransferase 2A-mediated succinylation of adenosine monophosphate-activated protein kinase suppresses cholelithiasis. This work not only provides novel mechanistic insights into cholelithiasis but also establishes succinylation as a promising therapeutic target, thereby addressing a critical knowledge gap in the field.

Keywords: Cholelithiasis; Succinylation; Lysine acetyltransferase 2A; Adenosine monophosphate-activated protein kinase; Protein post-translational modification

Core Tip: While the role of lysine succinylation, a significant post-translational modification, remains largely unexplored in the context of cholelithiasis, this investigation demonstrates that lysine acetyltransferase 2A-mediated succinylation of adenosine monophosphate-activated protein kinase suppresses cholelithiasis through modulation of the adenosine monophosphate-activated protein kinase/sirtuin 1 signaling axis, thereby attenuating inflammatory responses. These findings offer a transformative understanding of cholelithiasis pathogenesis and establish protein succinylation as a promising therapeutic target, effectively addressing a critical research void in this field.