Related Experiment Video
Updated: Jul 1, 2025

Characterization of MLKL-mediated Plasma Membrane Rupture in Necroptosis
Published on: August 7, 2018
Necroptosis and Its Involvement in Various Diseases
1Department of Biochemistry, Faculty of Medicine, Toho University School of Medicine, Tokyo, Japan. hiroyasu.nakano@med.toho-u.ac.jp.
Abstract:
Necroptosis is a regulated form of cell death involved in the development of various pathological conditions. In contrast to apoptosis, plasma membrane rupture (PMR) occurs in cells in the relatively early stage of necroptosis; therefore, necroptosis induces a strong inflammatory response. Stimuli, including tumor necrosis factor (TNF), interferon (IFN)α/β, lipopolysaccharide, polyI:C, and viral infection, induce the formation of necrosomes that lead to membrane rupture and the release of intracellular contents, termed danger-associated molecular patterns (DAMPs). DAMPs are the collective term for molecules that normally reside in the cytoplasm or nucleus in living cells without inducing inflammation but induce strong inflammatory responses when released outside cells. Recent studies have provided a better understanding of the mechanisms underlying PMR and the release of DAMPs. Moreover, necroptosis is involved in various pathological conditions, and mutations in necroptosis-related genes can cause hereditary autoinflammatory syndromes. Thus, manipulating necroptosis signaling pathways may be useful for treating diseases involving necroptosis.
Insights
Necroptosis, a regulated cell death, causes early plasma membrane rupture and releases danger-associated molecular patterns (DAMPs), driving inflammation. Understanding necroptosis mechanisms may offer new therapeutic strategies for related diseases.
Area of Science:
- Cellular biology
- Immunology
- Pathology
Background:
- Necroptosis is a regulated form of cell death.
- It is implicated in various pathological conditions.
- Necroptosis involves early plasma membrane rupture, leading to inflammation via danger-associated molecular patterns (DAMPs) release.
Purpose of the Study:
- To elucidate the mechanisms of plasma membrane rupture (PMR) in necroptosis.
- To understand the release of danger-associated molecular patterns (DAMPs).
- To explore the therapeutic potential of targeting necroptosis signaling pathways.
Main Methods:
- Review of recent studies on necroptosis mechanisms.
- Analysis of stimuli inducing necroptosis (e.g., TNF, viral infection).
- Investigation of necrosome formation and its role in PMR.
Main Results:
- Necroptosis triggers early plasma membrane rupture, distinct from apoptosis.
- The release of intracellular contents (DAMPs) from ruptured cells induces strong inflammatory responses.
- Mutations in necroptosis-related genes are linked to hereditary autoinflammatory syndromes.
Conclusions:
- Necroptosis is a key driver of inflammation through DAMPs release.
- Targeting necroptosis pathways presents a potential therapeutic avenue for diseases associated with this cell death process.
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...
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...
Apoptosis
Autophagic Cell Death
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and...
Phagocytosis of Apoptotic Cells
Normal cells contain receptors that prevent them from being recognized...
Caspases

