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Updated: Aug 8, 2025

Characterization of MLKL-mediated Plasma Membrane Rupture in Necroptosis
Published on: August 7, 2018
Mixed lineage kinase domain-like pseudokinase: Conventional (necroptosis) and unconventional
Tuna Onal1, Melike Ozgul-Onal2, Ilana Chefetz3
1Faculty of Medicine, Department of Histology and Embryology, Bandirma Onyedi Eylul University, Balikesir, Turkey; The Hormel Institute, University of Minnesota, Austin, MN, United States.
Abstract:
Mixed lineage kinase domain-like pseudokinase (MLKL) is the terminal and indispensable mediator of necroptosis. Necroptosis, also known as programmed cell necrosis, is a caspase-independent cell death mechanism involved in various pathologic and inflammatory processes. Triggering necroptosis could be an alternative approach in treating apoptosis-resistant cancer cells to prevent recurrent disease. In addition to its function in necroptosis, MLKL plays a role as a regulator in many cellular processes independent of necroptosis. A better understanding of the intracellular function of MLKL and its role in various diseases and pathologic conditions is needed to enable discovery of new targeted therapies. Various necroptosis-dependent and independent functions of MLKL are reviewed in this chapter, with a focus on functions of MLKL in necroptosis, autophagy, inflammation, tissue regeneration, and endosomal trafficking.
Insights
Mixed lineage kinase domain-like pseudokinase (MLKL) is crucial for programmed cell necrosis (necroptosis). Understanding MLKL
Area of Science:
- Molecular Biology
- Cellular Biology
- Pathology
Background:
- Mixed lineage kinase domain-like pseudokinase (MLKL) is the key mediator of necroptosis, a programmed cell death pathway.
- Necroptosis is a caspase-independent cell death mechanism implicated in inflammatory diseases and cancer.
- Targeting necroptosis offers a potential strategy against apoptosis-resistant cancers.
Purpose of the Study:
- To review the diverse intracellular functions of MLKL.
- To explore MLKL's roles in both necroptosis-dependent and independent cellular processes.
- To highlight MLKL's involvement in autophagy, inflammation, tissue regeneration, and endosomal trafficking.
Main Methods:
- Literature review of studies on MLKL function.
- Analysis of necroptosis signaling pathways.
- Examination of MLKL's role in various cellular processes.
Main Results:
- MLKL is essential for necroptosis execution.
- MLKL regulates cellular processes beyond necroptosis.
- MLKL is implicated in autophagy, inflammation, tissue repair, and endosomal dynamics.
Conclusions:
- MLKL possesses multifaceted roles in cellular functions.
- Further research into MLKL's functions can lead to novel therapeutic targets.
- Understanding MLKL is vital for developing new treatments for diseases involving necroptosis and inflammation.
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