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Updated: Feb 26, 2026

Live-cell Imaging of Lysosomal Membrane Permeabilization During Necroptosis
Published on: November 14, 2025
Necroptosis: (Last) Message in a Bubble
Peter Vandenabeele1, Franck Riquet2, Benjamin Cappe3
1Molecular Signaling and Cell Death Unit, VIB Inflammation Research Center, Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium; Methusalem Program, Ghent University, Ghent, Belgium.
Abstract:
RIPK3 kinase-mediated phosphorylation of MLKL pseudokinase is the execution event of necroptosis. Two independent reports-in Immunity (Yoon et al., 2017) and Cell (Gong et al., 2017)-reveal that MLKL affects homeostatic membrane trafficking and necroptosis-enhanced bubble formation involving interaction with the ESCRT machinery.
Insights
Receptor-interacting protein kinase 3 (RIPK3) triggers necroptosis by phosphorylating mixed lineage kinase domain-like pseudokinase (MLKL). MLKL also regulates membrane trafficking and bubble formation during necroptosis through ESCRT interactions.
Area of Science:
- Cellular biology
- Molecular biology
- Immunology
Background:
- Necroptosis is a regulated form of cell death.
- RIPK3-mediated phosphorylation of MLKL is a key event in necroptosis execution.
Purpose of the Study:
- To elucidate the role of MLKL beyond its function as a necroptosis executioner.
- To investigate the interaction of MLKL with cellular machinery during necroptosis.
Main Methods:
- The study references two independent reports (Yoon et al., 2017; Gong et al., 2017).
- Methods likely involved molecular biology and cell imaging techniques to study protein interactions and cellular events.
Main Results:
- MLKL plays a role in homeostatic membrane trafficking.
- MLKL is involved in necroptosis-enhanced bubble formation.
- MLKL interacts with the Endosomal Sorting Complexes Required for Transport (ESCRT) machinery.
Conclusions:
- MLKL has multifaceted roles in cellular processes, including both necroptosis execution and membrane trafficking.
- The interaction between MLKL and the ESCRT machinery is crucial for necroptotic membrane dynamics.
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