Molecular mechanisms of necroptosis: an ordered cellular explosion

  title={Molecular mechanisms of necroptosis: an ordered cellular explosion},
  author={Peter Vandenabeele and Lorenzo Galluzzi and Tom Vanden Berghe and Guido Kroemer},
  journal={Nature Reviews Molecular Cell Biology},
For a long time, apoptosis was considered the sole form of programmed cell death during development, homeostasis and disease, whereas necrosis was regarded as an unregulated and uncontrollable process. Evidence now reveals that necrosis can also occur in a regulated manner. The initiation of programmed necrosis, 'necroptosis', by death receptors (such as tumour necrosis factor receptor 1) requires the kinase activity of receptor-interacting protein 1 (RIP1; also known as RIPK1) and RIP3 (also… 

The role of necroptosis, an alternative form of cell death, in cancer therapy

The molecular mechanism of necroptosis is described and how it could be manipulated in the treatment of cancer is summarized.

[The molecular mechanism of necroptosis].

Then, damage-associated molecular pattern (DAMP) molecules were released from necroptosis cells, recognized and internalized by phagocytes, and the clearance of death cells was completed.

Role of necroptosis in the pathogenesis of solid organ injury

Novel insights into the involvement of necroptosis in specific injury of different organs, and the therapeutic platform that it provides for treatment are summarized.

Necroptosis: Biochemical, Physiological and Pathological Aspects

Necroptosis recently has been found to contribute to a wide range of pathologic cell death forms including ischemic brain injury, neurodegenerative diseases and viral infection, therefore a better understanding of the necroptotic signaling machinery has clinical relevance.

Necroptosis: A Novel Cell Death Modality and Its Potential Relevance for Critical Care Medicine.

The molecular mechanisms of necroptosis are discussed, the effect of inhibiting necroPTosis in experimental models of critical illnesses is analyzed, and the simultaneous targeting of multiple cell death modalities is discussed because, depending on the cell type and cellular conditions, various types of cell death may contribute to the pathology.

The Role of Necroptosis in Cardiovascular Disease

Necroptosis has been proposed as an important component to the pathophysiology of heart disease such as vascular atherosclerosis, ischemia-reperfusion injury, myocardial infarction and cardiac remodeling and Targeting necroptosis signaling pathways may provide therapeutic benefit in the treatment of cardiovascular diseases.

The role of necroptosis in disease and treatment

This review attempts to explore the therapeutic prospects of necroptosis regulators by describing its molecular mechanism and the role it played in pathological condition and tissue homeostasis, and to summarize the research and clinical applications of corresponding regulators.

Small-Molecule Inhibitors of Necroptosis

In this review, inhibitors of necroptosis that are currently being developed and additional possible targets for manipulation are discussed.

The mechanism of necroptosis in normal and cancer cells

  • S. Fulda
  • Biology, Medicine
    Cancer biology & therapy
  • 2013
New insights into the signaling networks involved in the regulation of necroptosis will likely have important implications for the exploitation of this form of programmed cell death for the diagnosis or treatment of many diseases.

Necroptosis: A Pathogenic Negotiator in Human Diseases

Several natural and chemical compounds and novel targeted therapies that elicit beneficial roles of necroptotic cell death in malignant cells to bypass apoptosis and drug resistance are discussed to provide suggestions for further research in this field.



Molecular mechanisms and pathophysiology of necrotic cell death.

This review will focus on the intracellular and intercellular signaling events in necrosis induced by different stimuli, such as oxidative stress, cytokines and pathogen-associated molecular patterns (PAMPs), which can be linked to several pathologies such as stroke, cardiac failure, neurodegenerative diseases, and infections.

Identification of RIP1 kinase as a specific cellular target of necrostatins.

Necroptosis is a cellular mechanism of necrotic cell death induced by apoptotic stimuli in the form of death domain receptor engagement by their respective ligands under conditions where apoptotic execution is prevented and necrostatins are established as the first-in-class inhibitors of RIP1 kinase, the key upstream kinase involved in the activation of necroptosis.

RIP3, an Energy Metabolism Regulator That Switches TNF-Induced Cell Death from Apoptosis to Necrosis

The protein kinase receptor-interacting protein 3 (RIP3) was identified as a molecular switch between TNF-induced apoptosis and necrosis in NIH 3T3 cells and found that RIP3 was required for necrosisin other cells.

TNFα and reactive oxygen species in necrotic cell death

The sensitization of virus-infected cells to TNFα indicates that necrotic cell death may represent an alternative cell death pathway for clearance of infected cells.

No death without life: vital functions of apoptotic effectors

The results corroborate the conjecture that any kind of protein that has previously been specifically implicated in apoptosis might have a phylogenetically conserved apoptosis-unrelated function, most likely as part of an adaptive response to cellular stress.

Necroptosis, necrosis and secondary necrosis converge on similar cellular disintegration features

Subcellular events during tumor necrosis factor-induced necroptosis, H2O2-induced necrosis and anti-Fas-induced secondary necrosis were studied using high-resolution time-lapse microscopy to characterize the cellular disintegration phase of the three types of necrosis.

Necrotic cell death and 'necrostatins': now we can control cellular explosion.

A Role for Tumor Necrosis Factor Receptor-2 and Receptor-interacting Protein in Programmed Necrosis and Antiviral Responses*

TNF-induced programmed necrosis is facilitated by TNFR-2 signaling and caspase inhibition and may play a role in controlling viral infection.

Tumor necrosis factor can induce both apoptic and necrotic forms of cell lysis.

Time-lapse video microscopy is used to observe the death of several TNF-sensitive target cell lines while measuring the release of Na2(51)CrO4 and [3H]TdR from cytoplasmic and nuclear compartments, respectively, and finds that the type of cell death observed depends on the cell being tested.