Apoptosis is programmed and tidy; necrosis is accidental and inflammatory
Mnemonic
“Apoptosis is a quiet suicide; necrosis is a messy murder”:
| Apoptosis | Necrosis | |
|---|---|---|
| Energy | ATP dependent | Passive |
| Extent | Single cells | Groups of cells |
| Membrane | Intact, blebs | Ruptured |
| Contents | Retained in apoptotic bodies | Spilled |
| Inflammation | None | Marked |
| Physiological | Often | Never |
Two pathways converge on the caspases:
- Intrinsic (mitochondrial) - triggered by DNA damage, withdrawal of growth factors, or hypoxia. Regulated by BCL-2 (anti-apoptotic) and BAX (pro-apoptotic), releasing cytochrome c
- Extrinsic (death receptor) - Fas and TNF receptor ligation
Failure of apoptosis causes cancer, which is why BCL-2 overexpression defines follicular lymphoma and why p53 loss is so oncogenic; excessive apoptosis contributes to neurodegeneration and to CD4 loss in HIV.
Expansion
| Feature | Apoptosis | Necrosis |
|---|---|---|
| Nature | Programmed, physiological or pathological | Accidental, always pathological |
| Energy | ATP required | ATP depleted |
| Cell size | Shrinks | Swells |
| Membrane | Intact, then blebs | Ruptures |
| Contents | Packaged into apoptotic bodies | Spill out |
| Inflammation | None | Marked |
| Extent | Single cells | Sheets of cells |
Apoptotic pathways
- Intrinsic (mitochondrial): triggered by DNA damage, hypoxia or growth factor withdrawal; p53 promotes it, Bcl-2 inhibits it; cytochrome c release activates caspase 9
- Extrinsic (death receptor): Fas and TNF receptor, activating caspase 8
Both converge on the executioner caspases.
Physiological roles include embryonic digit separation, removal of self-reactive lymphocytes and endometrial shedding.
Disordered regulation causes disease: too little apoptosis in cancer (Bcl-2 overexpression in follicular lymphoma, p53 mutation in most cancers) and autoimmunity; too much in neurodegeneration and ischaemia-reperfusion injury.