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Apoptosis: Intrinsic and Extrinsic Pathways

Death receptor (extrinsic) and mitochondrial (intrinsic) routes converge on caspase-3 execution.

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Apoptosis: Intrinsic and Extrinsic Pathways

Apoptosis: Intrinsic and Extrinsic PathwaysTwo upstream routes activate initiator caspases and converge on caspase-3 executionExtrinsic PathwayIntrinsic PathwayBCL-2 familyAnti-apoptotic:BCL-2, BCL-XLPro-apoptotic:Bax, Bak, BIDBID cleavage amplifiesFasL / TNFDeath ligandDeath ReceptorFas / TNFR1FADDAdaptor proteinCaspase-8Initiator (extrinsic)DNA Damagep53 activatedBax / BakPro-apoptotic poresCytochrome cReleased from mitoCaspase-9Initiator (intrinsic)Caspase-3Executioner caspaseDNA fragmentationCytoskeletal cleavageMembrane blebbing(CAD endonuclease)(PARP, lamin cleavage)(apoptotic bodies formed)

Two parallel cascades: extrinsic (FasL/TNF -> death receptor -> FADD -> caspase-8) and intrinsic (DNA damage -> p53 -> Bax/Bak -> mitochondrial outer membrane permeabilization -> cytochrome-c -> apoptosome -> caspase-9). Both converge on caspase-3 cleaving structural and DNA-fragmentation targets.

Good for

  • Cancer biology and chemotherapy mechanism articles
  • Immunology and immune cell death explainers
  • Neurodegeneration and cell survival pathway content

Source & accuracy

This apoptosis: intrinsic and extrinsic pathways is an editorial illustration built to represent the concept accurately. Where it shows figures, they are typical or representative values chosen to make the relationship clear, not a single underlying dataset. The diagram and its explainer are reviewed and maintained centrally, and updated over time as understanding improves.

The extrinsic and intrinsic routes to cell death

Apoptosis can be triggered by two distinct routes that converge on the same machinery. The extrinsic pathway begins at the cell surface, where death-signal molecules bind death receptors (such as Fas and TNF receptors) and assemble a complex that activates initiator caspases. It is often how immune signals instruct a target cell to self-destruct.

The intrinsic, or mitochondrial, pathway responds to internal stress such as DNA damage, oxidative stress, or growth-factor withdrawal. These signals tip the balance of Bcl-2 family proteins, allowing pore-forming proteins to release cytochrome c from mitochondria, which assembles the apoptosome and activates caspase-9.

Where the pathways meet

Both routes funnel into executioner caspases, especially caspase-3, which carry out the actual dismantling of the cell by cleaving structural and regulatory proteins. The two pathways can also talk to each other, so they are not fully isolated.

Because faulty apoptosis contributes to cancer (too little) and to degenerative conditions (too much), these pathways are heavily studied as drug targets. This is general educational information about cell biology, not medical advice.

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Reference

What this is
A free, embeddable, animated apoptosis: intrinsic and extrinsic pathways for any website.
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