Related Experiment Video
Updated: Mar 22, 2026
Characterization of MLKL-mediated Plasma Membrane Rupture in Necroptosis
Published on: August 7, 2018
How are necrotic cells recognized by their predators?
Zao Li1, Zheng Zhou1
1Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine , Houston, TX, USA.
Abstract:
Necrosis is a type of cell death often caused by cell injury and is linked to human diseases including neuron degeneration, stroke, and cancer. Cells undergoing necrosis are engulfed and degraded by engulfing cells, their predators. The mechanisms by which necrotic cells are recognized and removed remain elusive. Here we comment on our recent findings that reveal new molecular mechanisms of necrotic-cell recognition. Through studying the C. elegans touch neurons undergoing excitotoxic necrosis, we identified a receptor/ligand pair that enables engulfing cells to recognize necrotic neurons. The phagocytic receptor CED-1 is activated through interaction with its ligand phosphatidylserine (PS), exposed on the surface of necrotic cells. Furthermore, against the common belief that necrotic cells have ruptured plasma membrane, we found that necrotic C. elegans touch neurons actively present PS on their outer surfaces while maintaining plasma membrane integrity. We further identified 2 mechanisms governing the presentation of PS, one of which is shared with cells undergoing apoptosis, a "cell suicide" event, whereas the other is unique to necrotic neurons. The influx of Ca(2+), a key necrosis-triggering factor, is implicated in activating a neuronal PS-scramblase for PS exposure. We propose that the mechanisms controlling PS-exposure and necrotic-cell recognition by engulfing cells are likely conserved from worms to humans.
Insights
Necrotic cells are recognized by engulfing cells via phosphatidylserine (PS) exposure, a process crucial for clearing dead cells. This study reveals novel molecular mechanisms for this recognition, conserved across species.
Area of Science:
- Cell Biology
- Neuroscience
- Developmental Biology
Background:
- Necrosis, a cell death mode from injury, is implicated in diseases like cancer and neurodegeneration.
- Efficient removal of necrotic cells by engulfing cells is vital, but recognition mechanisms are unclear.
- Understanding necrotic cell clearance is crucial for developing therapies for related human diseases.
Purpose of the Study:
- To elucidate the molecular mechanisms by which engulfing cells recognize and clear necrotic cells.
- To identify the specific receptor-ligand interactions involved in necrotic cell recognition.
- To investigate the mechanisms of phosphatidylserine exposure in necrotic cells.
Main Methods:
- Utilized C. elegans touch neurons undergoing excitotoxic necrosis as a model system.
- Investigated the role of the phagocytic receptor CED-1 and its ligand phosphatidylserine (PS).
- Analyzed plasma membrane integrity and phosphatidylserine exposure during necrosis.
Main Results:
- Identified the CED-1/phosphatidylserine (PS) pair as key for necrotic neuron recognition.
- Demonstrated that necrotic neurons expose PS while maintaining plasma membrane integrity.
- Discovered two distinct mechanisms for PS exposure in necrosis, one shared with apoptosis and one unique.
Conclusions:
- The CED-1/phosphatidylserine interaction is a conserved mechanism for necrotic cell recognition.
- Necrotic cells actively regulate PS exposure, challenging previous assumptions about membrane rupture.
- Calcium influx plays a role in activating PS scramblase for PS exposure during necrosis.
Related Concept Videos
01:16Necrosis
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...
01:17Phagocytosis of Apoptotic Cells
Normal cells contain receptors that prevent them from being recognized...
01:30Overview 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...
01:28Cells of the Innate Immune Response
Phagocytes
Phagocytes police the peripheral tissues by removing cellular debris and responding to the invasion of foreign substances or pathogens. Many phagocytes attack and remove microorganisms even before lymphocytes detect them. The human body has two general...
01:25Immune Surveillance by NK Cells and Phagocytes
Natural Killer Cells: The Fast Responders
NK cells are large granular lymphocytes found in the blood and lymphatic system. These...
01:28Microbial Interactions: Predation