Reviews

< Previous         Next >  
The molecular mechanisms of MLKL-dependent and MLKL-independent necrosis
Lu Li1,† , An Tong2,† , Qiangsheng Zhang1 , Yuquan Wei1 , Xiawei Wei1,*
1Laboratory of Aging Research and Cancer Drug Target, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu 610041, China
2Department of Gynecology and Obstetrics, Development and Related Disease of Women and Children Key Laboratory of Sichuan Province, Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, West China Second Hospital, and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China
These authors contributed equally to this work.
*Correspondence to:Xiawei Wei , Email:xiaweiwei@scu.edu.cn
J Mol Cell Biol, Volume 13, Issue 1, January 2021, Pages 3-14  https://doi.org/10.1093/jmcb/mjaa055
Keyword: MLKL, necrosis, necroptosis, mechanism, diseases

Necrosis, a type of unwanted and passive cell demise, usually occurs under the excessive external stress and is considered to be unregulated. However, under some special conditions such as caspase inhibition, necrosis is regulable in a well-orchestrated way. The term ‘regulated necrosis’ has been proposed to describe such programed necrosis. Recently, several forms of necrosis, including necroptosis, pyroptosis, ferroptosis, parthanatos, oxytosis, NETosis, and Na+/K+-ATPase-mediated necrosis, have been identified, and some crucial regulators governing regulated necrosis have also been discovered. Mixed lineage kinase domain-like pseudokinase (MLKL), a core regulator in necroptosis, acts as an executioner in response to ligands of death receptor family. Its activation requires the receptor-interacting protein kinases, RIP1 and RIP3. However, MLKL is only involved in necroptosis, i.e. MLKL is dispensable for necrosis. Therefore, this review is aimed at summarizing the molecular mechanisms of MLKL-dependent and MLKL-independent necrosis.