Related Experiment Video
Updated: Jul 25, 2025

Characterization of MLKL-mediated Plasma Membrane Rupture in Necroptosis
Published on: August 7, 2018
The Many Faces of MLKL, the Executor of Necroptosis
Veronica Martinez-Osorio1, Yasmin Abdelwahab1, Uris Ros1
1Institute for Genetics and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, 50931 Cologne, Germany.
Abstract:
Necroptosis is a recently discovered form of regulated cell death characterized by the disruption of plasma membrane integrity and the release of intracellular content. Mixed lineage kinase domain-like (MLKL) protein is the main player of this cell death pathway as it mediates the final step of plasma membrane permeabilization. Despite the significant progress in our knowledge of the necroptotic pathway and MLKL biology, the precise mechanism of how MLKL functions remain unclear. To understand in what way MLKL executes necroptosis, it is crucial to decipher how the molecular machinery of regulated cell death is activated in response to different stimuli or stressors. It is also indispensable to unveiling the structural elements of MLKL and the cellular players that are required for its regulation. In this review, we discuss the key steps that lead to MLKL activation, possible models that explain how it becomes the death executor in necroptosis, and its emerging alternative functions. We also summarize the current knowledge about the role of MLKL in human disease and provide an overview of existing strategies aimed at developing new inhibitors that target MLKL for necroptosis intervention.
Insights
Necroptosis, a regulated cell death, involves the MLKL protein permeabilizing the plasma membrane. This review explores MLKL activation, its role in disease, and therapeutic strategies targeting this cell death pathway.
Area of Science:
- Cell Biology
- Molecular Biology
- Immunology
Background:
- Necroptosis is a regulated form of cell death involving plasma membrane rupture and cellular content release.
- The Mixed Lineage Kinase Domain-Like (MLKL) protein is essential for the final execution of necroptosis, causing membrane permeabilization.
Purpose of the Study:
- To elucidate the precise mechanisms by which MLKL executes necroptosis.
- To understand MLKL activation pathways in response to various stimuli.
- To explore MLKL's structural elements, regulatory cellular players, and alternative functions.
Main Methods:
- Literature review of necroptosis and MLKL biology.
- Analysis of current models for MLKL activation and function.
- Summary of MLKL's role in human diseases.
Main Results:
- MLKL is the key effector mediating plasma membrane permeabilization in necroptosis.
- Understanding MLKL activation requires deciphering upstream signaling and regulatory components.
- MLKL possesses emerging alternative functions beyond its role in necroptosis.
Conclusions:
- MLKL activation is a critical step in necroptosis, but its precise execution mechanism requires further investigation.
- MLKL's involvement in human diseases highlights its therapeutic potential.
- Developing MLKL inhibitors is a promising strategy for necroptosis intervention.
More Related Videos
09:15Tyramide Signal Amplification for the Immunofluorescent Staining of ZBP1-Dependent Phosphorylation of RIPK3 and MLKL After HSV-1 Infection in Human Cells
Published on: October 20, 2022
10:10Use of Two Dimensional Semi-denaturing Detergent Agarose Gel Electrophoresis to Confirm Size Heterogeneity of Amyloid or Amyloid-like Fibers
Published on: April 26, 2018
Related Concept Videos
Necrosis
Morphological Manifestations of Necrosis
Necrotic cells show different types of morphological appearance depending on the type of tissue and infection. In coagulative necrosis, cells become...
The Extrinsic Apoptotic Pathway
The Intrinsic Apoptotic Pathway
Overview of Cell Death
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the...
Caspases
Autophagic Cell Death
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and...