Liang MX, Zhou Y, Li SQ, Xiang WS, Pan ZQ, Chen YH, He YH. Mixed lineage kinase domain-like protein in liver diseases: Cell-type-specific functions and dual roles. World J Gastroenterol 2025; 31(14): 104523 [DOI: 10.3748/wjg.v31.i14.104523]
Corresponding Author of This Article
Yi-Huai He, MD, Doctor, Department of Infectious Diseases, Affiliated Hospital of Zunyi Medical University, No. 149 Dalian Road, Huichuan District, Zunyi 563000, Guizhou Province, China. 993565989@qq.com
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Letter to the Editor
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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: http://creativecommons.org/licenses/by-nc/4.0/
Ming-Xing Liang, Ying Zhou, Su-Qun Li, Wan-Sheng Xiang, Ying-Hua Chen, Yi-Huai He, Department of Infectious Diseases, Affiliated Hospital of Zunyi Medical University, Zunyi 563000, Guizhou Province, China
Zong-Qin Pan, Department of Infectious Diseases, People’s Hospital Qiandongnan Miao and Dong Autonomous Prefecture, Kaili 556000, Guizhou Province, China
Co-first authors: Ming-Xing Liang and Ying Zhou.
Author contributions: Liang MX, Zhou Y, Li SQ, Xiang WS, Pan ZQ, Chen YH, and He YH contributed to this paper; Liang MX, Zhou Y, and He YH designed the overall concept and outline of the manuscript, contributed to the writing, and editing the manuscript and review of literature; Li SQ, Xiang WS, Pan ZQ, and Chen YH contributed to the discussion and design of the manuscript; He YH revised the manuscript; All authors have read and approved the final manuscript.
Supported by the Science and Technology Planning Projects of Guizhou Province, No. QKHJC-ZK[2022]YB642; Health Research Project of Guizhou Province, No. gzwkj2024-324, and No. gzwkj2024-103; WBE Liver Fibrosis Foundation, No. CFHPC2025028; Beijing Liver and Gallbladder Mutual Aid Public Welfare Foundation Artificial Liver Special Fund, No. iGandanF-1082024-Rgg018; and Student Innovation and Entrepreneurship Training Program of Zunyi Medical University, No. S2024106612360.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
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: Yi-Huai He, MD, Doctor, Department of Infectious Diseases, Affiliated Hospital of Zunyi Medical University, No. 149 Dalian Road, Huichuan District, Zunyi 563000, Guizhou Province, China. 993565989@qq.com
Received: December 24, 2024 Revised: February 25, 2025 Accepted: March 13, 2025 Published online: April 14, 2025 Processing time: 108 Days and 22.1 Hours
Abstract
In this letter, we comment on the article by Xuan Yuan et al, published in the recent issue of the World Journal of Gastroenterology. Mixed lineage kinase domain-like protein (MLKL) exhibits cell-type-specific functions in liver parenchymal and non-parenchymal cells, playing dual roles in the pathogenesis of liver diseases. In hepatocytes, MLKL primarily mediates necroptosis and inhibits autophagy, thereby exacerbating liver injury. Conversely, in non-parenchymal liver cells, MLKL modulates inflammatory responses and promotes fibrotic processes, thereby driving disease progression. Notably, MLKL also demonstrates protective functions under specific conditions. For instance, MLKL can inhibit intracellular bacterial replication, promote endosomal trafficking, and facilitate the generation and release of extracellular vesicles, potentially exerting hepatoprotective effects. Understanding these cell-type-specific mechanisms of MLKL action, including its dual roles in promoting injury and providing protection, is crucial for elucidating the complex pathogenesis of liver diseases and developing targeted therapeutic strategies.
Core Tip: Mixed lineage kinase domain-like protein (MLKL) functions to mediate necroptosis, inhibit autophagy, and regulate inflammatory responses. The MLKL exhibits different functions in various types of liver cells, leading to diverse manifestations of different liver diseases. This complexity not only brings challenges in understanding the roles of MLKL in liver diseases, but also presents an obstacle in developing therapeutic strategies for targeting MLKL. Here, we briefly review the functions of MLKL and analyze its specific roles in different types of liver cells, aiming to provide clear strategies for precisely targeting MLKL in the treatment of liver diseases.
