General pathology · Cell injury, adaptation and death
Other forms of cell death: necroptosis, pyroptosis, ferroptosis !
- Mechanism
Some cells burst open on purpose. These planned but messy deaths alarm the immune system and matter in infection and inflammation.
Updated 2026-11-01
What it is
Besides apoptosis and accidental necrosis, cells can die by programs that end with membrane rupture and inflammation. Necroptosis is a backup pathway when caspase 8 is blocked; pyroptosis follows inflammasome activation and releases IL-1β; ferroptosis is iron-dependent death by lipid peroxidation. They are active research areas in sepsis, ischemia, neurodegeneration and cancer.
Key facts
- Necroptosis looks like necrosis under the microscope but depends on a signalling program.
- Several viruses carry caspase inhibitors; necroptosis may be the host’s answer.
- Urate crystals in gout and mutated pyrin in familial Mediterranean fever activate inflammasomes and IL-1β release.
Regulated forms of cell death compared
| Form | Trigger | Key molecules | Result |
|---|---|---|---|
| Apoptosis (reference) | DNA damage, death ligands | BCL-2 family, caspases 8, 9, 3 | Shrinking, no inflammation |
| Necroptosis | TNF or viral infection with caspase 8 blocked | RIPK1, RIPK3, MLKL | Rupture, inflammation |
| Pyroptosis | Microbial products or crystals sensed by inflammasomes | Caspase 1, gasdermin D, IL-1β, IL-18 | Rupture, fever, strong inflammation |
| Ferroptosis | Loss of lipid peroxide defences, free iron | GPX4, glutathione, iron | Membrane lipid damage, rupture |
| NETosis | Neutrophil activation by microbes | Peptidyl arginine deiminase 4, histones, DNA | Extracellular traps; may promote thrombosis |
Clinical notes
- IL-1 blocking drugs are used in some autoinflammatory diseases driven by inflammasome activation.
- In sepsis, pyroptosis and NETs are thought to contribute to inflammation, coagulation and organ dysfunction.
Test yourself
Think of the answer, then tap the question to see it.
Which proteins carry out necroptosis?
RIPK1, RIPK3 and the pore-forming protein MLKL, typically when caspase 8 is inhibited.
What does caspase 1 do in pyroptosis?
It cleaves gasdermin D, which forms membrane pores, and processes pro-IL-1β and pro-IL-18 into active cytokines.
What drives ferroptosis?
Iron-dependent peroxidation of membrane lipids when glutathione peroxidase 4 or glutathione is insufficient.
Related
- Apoptosis: the intrinsic and extrinsic pathways
- Apoptosis vs necrosis: the comparison table
- Oxidative stress and free-radical injury
- Mediators of inflammation: the table to know
- How septic shock develops
Related conditions
- Sepsis and septic shock
- Familial Mediterranean fever and other hereditary autoinflammatory syndromes
- Gout
- Acute pancreatitis
- Myocardial Infarction (Heart Attack)
- Ischaemic stroke
Elsewhere in DurgiPedia
- Pattern recognition: PAMPs, DAMPs, Toll-like receptors
- Innate immunity (overview, barriers)
- Interleukin-1
- Neutrophil
- Glutathione peroxidase (GPX)
- Iron metabolism
Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.
Sources: Sepsis: MedlinePlus (MedlinePlus, US National Library of Medicine, 2024); MEFV gene: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2024); 4.6 Tissue Injury and Aging (OpenStax (Rice University), 2022).
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Representative model, for educational purposes only.