CorpusHuman Anatomy
Cells & TissuesCell process

Apoptosis

Also known as: programmed cell death, caspases, BCL-2, cytochrome c, Fas, apoptosome

Programmed, energy-dependent cell death executed by caspases, in which the cell shrinks and fragments into membrane-bound apoptotic bodies that are phagocytosed without inflammation.

Overview

DNA fragment sizeMultiples of ≈180–200 bp
Initiator caspases8 (extrinsic), 9 (intrinsic)
Executioner caspases3, 7

Morphology: cell shrinkage with dense eosinophilic cytoplasm; chromatin condensation (pyknosis) and nuclear fragmentation (karyorrhexis); plasma-membrane blebbing and formation of apoptotic bodies. Endonucleases cut DNA between nucleosomes, giving a "ladder" of ≈180–200-bp multiples on gel electrophoresis (TUNEL staining in tissue). Phosphatidylserine flips to the outer leaflet as an "eat me" signal (detected by annexin V), so neighbouring cells and macrophages engulf the bodies quickly — the membrane stays intact, contents are not released and there is no inflammation.

The intrinsic (mitochondrial) pathway responds to DNA damage (via p53), growth-factor withdrawal, misfolded proteins and other stress. Pro-apoptotic BH3-only proteins (BIM, BID, PUMA, NOXA) overcome the anti-apoptotic BCL-2 and BCL-xL and activate BAX and BAK, which permeabilise the outer mitochondrial membrane. Cytochrome c is released and binds Apaf-1 to form the apoptosome, which activates initiator caspase-9; SMAC/DIABLO neutralises inhibitor-of-apoptosis proteins (IAPs). The extrinsic (death-receptor) pathway starts when Fas ligand binds Fas (CD95) or TNF binds TNFR1: the death domains recruit FADD, forming the death-inducing signalling complex that activates initiator caspase-8 (cleavage of BID links it to the intrinsic pathway). Both converge on executioner caspases 3 and 7, cysteine proteases that cleave hundreds of substrates (lamins, cytoskeletal proteins, ICAD releasing the DNase). Cytotoxic T and NK cells also kill by perforin/granzyme B.

Physiological apoptosis sculpts the embryo (interdigital webs, lumen formation), eliminates self-reactive lymphocytes in the thymus, removes cells after hormone withdrawal (endometrial shedding, regression of the lactating breast), ends immune responses and balances proliferation in renewing tissues.

Parts & subdivisions

  1. Intrinsic (mitochondrial) pathway
    BCL-2 family → BAX/BAK → cytochrome c → apoptosome → caspase-9.
  2. Extrinsic (death-receptor) pathway
    FasL/Fas or TNF/TNFR1 → FADD → caspase-8.
  3. Executioner caspases
    Caspase-3 and -7 dismantle the cell.
  4. Perforin/granzyme pathway
    Cytotoxic T cells and NK cells inject granzyme B, activating caspases directly.

Anatomy

Histology

Single shrunken, intensely eosinophilic cells with dense or fragmented nuclei, often surrounded by a clear halo (e.g. Councilman bodies in viral hepatitis, "dyskeratotic" keratinocytes).

Function

  • Removes unwanted, damaged or dangerous cells without inflammation.
  • Shapes tissues during development.
  • Maintains cell-number homeostasis and immune tolerance.

Clinical significance

Too little apoptosis

Follicular lymphoma — t(14;18) places BCL2 under the immunoglobulin heavy-chain promoter; venetoclax (BCL-2 inhibitor) treats CLL. Autoimmune lymphoproliferative syndrome — Fas or FasL defects. Loss of p53 lets damaged cells survive.

Too much apoptosis

Neurodegenerative diseases, ischaemia–reperfusion injury (penumbra of infarcts), loss of CD4⁺ T cells in HIV infection, graft-versus-host disease.

Test yourself

In the intrinsic pathway of apoptosis, which mitochondrial protein binds Apaf-1 to form the apoptosome?
  1. BCL-2
  2. Cytochrome c
  3. Fas ligand
  4. Ubiquitin

Answer: Cytochrome c

BAX/BAK permeabilise the outer mitochondrial membrane, releasing cytochrome c, which with Apaf-1 and procaspase-9 forms the apoptosome; caspase-9 activates executioner caspases 3 and 7. BCL-2 prevents this; Fas ligand triggers the extrinsic (caspase-8) pathway.

Which of the following is characteristic of apoptosis rather than necrosis?
  1. Cell swelling and membrane rupture
  2. Marked acute inflammation
  3. Membrane blebbing, apoptotic bodies and DNA laddering
  4. Release of cell contents into the interstitium

Answer: Membrane blebbing, apoptotic bodies and DNA laddering

Apoptosis is an energy-dependent, caspase-mediated programme: shrinkage, chromatin condensation (pyknosis), internucleosomal DNA cleavage (≈180–200 bp ladder), blebbing and phagocytosis of apoptotic bodies, with no inflammation.

More cells & tissues questions

Compiled from standard anatomy and physiology references — see the Cells & Tissues sources. For education only; not medical advice.