Related Experiment Video
Updated: Jul 15, 2026
08:55
Characterization of MLKL-mediated Plasma Membrane Rupture in Necroptosis
Published on: August 7, 2018
Optimized strategies for necroptosis induction and evaluation.
Jie Lu1, Haohao Lu1, Sudan He1
1State Key Laboratory of Common Mechanism Research for Major Diseases, and CAMS Key Laboratory of Synthetic Biology Regulatory Elements, Suzhou Institute of Systems Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Suzhou, Jiangsu, P.R. China.
Methods in Cell Biology
|July 13, 2026
Summary
Necroptosis, a regulated cell death, involves RIPK3-mediated MLKL phosphorylation, leading to cell lysis. This study details methods to induce and detect necroptosis via TNF, TLR, and IFN pathways, aiding research into this cell death mechanism.
Area of Science:
- Biochemistry
- Cell Biology
- Immunology
Background:
- Necroptosis is a programmed form of lytic cell death.
- It is executed by receptor-interacting serine/threonine-protein kinase 3 (RIPK3) and mixed-lineage kinase domain-like pseudokinase (MLKL).
- Activation leads to plasma membrane rupture and release of damage-associated molecular patterns (DAMPs).
Purpose of the Study:
- To outline methods for inducing necroptosis.
- To describe techniques for detecting and validating necroptotic activity.
- To provide a comprehensive overview of necroptosis induction and evaluation strategies.
Main Methods:
- Induction of necroptosis via tumor necrosis factor receptor 1 (TNFR1) signaling.
- Activation of necroptosis through Toll-like receptors (TLR3/4) and interferon receptor pathways.
- Detection and validation of necroptosis using specific inhibitors and optimized protocols.
Main Results:
- Demonstrated convergence of multiple signaling pathways on RIPK3 activation.
- Showcased MLKL phosphorylation as the key event driving necroptosis.
- Established protocols for reliable induction and detection of necroptosis.
Conclusions:
- Necroptosis induction can be achieved through TNFR1, TLR, and interferon receptor pathways.
- RIPK3-mediated MLKL phosphorylation is central to necroptotic execution.
- The described methods facilitate robust research into necroptosis mechanisms and modulation.
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