Curriculum
Module 12 · 65 min
Cell Death Pathways
Apoptosis, necroptosis, pyroptosis, ferroptosis — and why the difference matters clinically.
CoreClinicalResearch
Topics
What this module covers
- 01Apoptosis: intrinsic (mitochondrial) and extrinsic (death-receptor) pathways
- 02Bcl-2 family: BH3-only sensors, multi-domain effectors (BAX/BAK), guardians (Bcl-2/xL/Mcl-1)
- 03Caspase cascade and apoptotic body clearance
- 04Necroptosis: RIPK1/RIPK3/MLKL
- 05Pyroptosis: inflammasome → caspase-1 → gasdermin D pore
- 06Ferroptosis: GPX4, lipid peroxidation, iron
- 07Immunogenic vs tolerogenic cell death
Deep dives
Lesson sub-pages
Learning objectives
By the end of this module you will be able to
- L01Distinguish death modalities by morphology, mediators, and immunological consequence.
- L02Explain how venetoclax (BCL-2 inhibitor) achieves selective tumour killing.
- L03Discuss when cell death is therapeutic, pathologic, or both.
Expected takeaways
What you should walk away believing
- →Apoptosis is silent; necroptosis, pyroptosis and ferroptosis are inflammatory.
- →Cancers up-regulate Bcl-2 family guardians; BH3-mimetics tip the balance to death.
- →Ferroptosis is a major emerging axis in neurodegeneration, ischaemia-reperfusion, and resistant cancer.
Core summary
At the Core level
Cells die in regulated ways — and the way they die matters because each mode produces different signals to the immune system. Apoptotic cells are silently cleared by efferocytosis; pyroptotic and necroptotic cells release DAMPs and inflame the tissue. Therapeutics now both induce death (oncology) and block it (neurodegeneration trials).
Myth vs reality
Common misconception
Claim
Apoptosis and necrosis are the only two ways cells die.
Reality
At least a dozen regulated death modalities are now recognised (necroptosis, pyroptosis, ferroptosis, NETosis, cuproptosis, parthanatos, entosis, lysosomal cell death).
Evidence-graded claims
Claims, scored A–F
A
Venetoclax + azacitidine improves AML survival in older adults
VIALE-A confirmed; standard of care.
F
Caspase inhibition improves sepsis survival
Trials negative; redundant death pathways take over.
C
Ferroptosis induction will be a major oncology modality
Promising preclinical; clinical proof-of-concept pending.
Quiz
Check your understanding
Q1. Pyroptosis effector pore is formed by:
Q2. Venetoclax targets:
Flashcards
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Front
Two arms of intrinsic apoptosis sensors?
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Suggested reading
Primary literature
- Molecular mechanisms of cell death: recommendations 2018 — Galluzzi et al., Cell Death Differ 2018 ↗
- Ferroptosis: an iron-dependent form of nonapoptotic cell death — Dixon et al., Cell 2012 ↗