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Updated: Jul 18, 2026
Characterization of MLKL-mediated Plasma Membrane Rupture in Necroptosis
Published on: August 7, 2018
Cell death by necrosis: towards a molecular definition
Pierre Golstein1, Guido Kroemer
1Centre d'Immunologie de Marseille-Luminy, Université de la Méditerranée, Case 906, 13288 Marseille Cedex 9, France.
Abstract:
Necrosis has been defined as a type of cell death that lacks the features of apoptosis and autophagy, and is usually considered to be uncontrolled. Recent research suggests, however, that its occurrence and course might be tightly regulated. After signaling- or damage-induced lesions, necrosis can include signs of controlled processes such as mitochondrial dysfunction, enhanced generation of reactive oxygen species, ATP depletion, proteolysis by calpains and cathepsins, and early plasma membrane rupture. In addition, the inhibition of specific proteins involved in regulating apoptosis or autophagy can change the type of cell death to necrosis. Because necrosis is prominent in ischemia, trauma and possibly some forms of neurodegeneration, further biochemical comprehension and molecular definition of this process could have important clinical implications.
Insights
Necrosis, often seen as uncontrolled cell death, is now understood to involve regulated processes. Understanding these molecular mechanisms of necrosis is crucial for potential clinical applications.
Area of Science:
- Biochemistry
- Cell Biology
- Molecular Biology
Background:
- Necrosis is traditionally defined as uncontrolled cell death, distinct from apoptosis and autophagy.
- Emerging evidence indicates that necrosis may involve regulated cellular mechanisms.
Purpose of the Study:
- To explore the regulated nature of necrosis.
- To understand the biochemical and molecular underpinnings of necrosis.
Main Methods:
- Review of recent research on cell death pathways.
- Analysis of molecular events during necrosis, including mitochondrial dysfunction and protein activity.
Main Results:
- Necrosis can exhibit controlled processes like mitochondrial dysfunction, reactive oxygen species generation, and specific proteolysis.
- Inhibition of apoptosis or autophagy regulators can induce necrosis.
- Key events include ATP depletion and early plasma membrane rupture.
Conclusions:
- Necrosis is not always uncontrolled and involves regulated molecular pathways.
- Further biochemical and molecular definition of necrosis is essential for clinical relevance, particularly in conditions like ischemia, trauma, and neurodegeneration.
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