Basic Study
Copyright ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Surg. Jun 27, 2025; 17(6): 106777
Published online Jun 27, 2025. doi: 10.4240/wjgs.v17.i6.106777
Mitochondrial alanyl-tRNA synthetase 2 mediates histone lactylation to promote ferroptosis in intestinal ischemia-reperfusion injury
Wei Dong, San-Xiong Huang, Mo-Liang Qin, Zhuo Pan
Wei Dong, Mo-Liang Qin, Zhuo Pan, Department of Hepatobiliary Pancreatic Surgery, Huzhou First People's Hospital, Huzhou 313000, Zhejiang Province, China
San-Xiong Huang, Department of Hepatobiliary Surgery, The First People’s Hospital of Huzhou, Huzhou 313000, Zhejiang Province, China
Author contributions: Dong W, Huang SX, Qin ML, and Pan Z designed the research study; Dong W, Huang SX, Qin ML, and Pan Z performed the research.
Institutional animal care and use committee statement: Animal experiments were approved by the Research Ethics Committee of Huzhou First People's Hospital.
Conflict-of-interest statement: The authors declare that they have no competing interests.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Data sharing statement: No additional data are available.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Zhuo Pan, Chief Physician, Department of Hepatobiliary Pancreatic Surgery, Huzhou First People's Hospital, No. 158 Back Plaza Road, Huzhou 532322, Zhejiang Province, China. m18267851073@163.com
Received: March 11, 2025
Revised: April 3, 2025
Accepted: May 12, 2025
Published online: June 27, 2025
Processing time: 80 Days and 20.8 Hours
Core Tip

Core Tip: This investigation reveals mitochondrial alanyl-tRNA synthetase 2 (AARS2) as a pivotal regulator of ferroptotic cell death in intestinal ischemia-reperfusion (I/R) injury. Our findings demonstrate that AARS2 augments histone H3K18 lactylation modification, which subsequently drives the transcriptional upregulation of acyl-CoA synthetase long-chain family member 4 through chromatin remodeling. This molecular cascade potentiates the accumulation of lipid peroxidation products and exacerbates intestinal epithelial damage. Pharmacological inhibition of AARS2 effectively suppresses ferroptosis progression and maintains mucosal barrier integrity, establishing its clinical relevance for managing I/R-associated tissue injury.