Intrinsic pathway ( mitochondrial pathway)

 

 1. Anti-Apoptotic ( BCL2 , BCLX ) . They posses four BH domain called BH1-4 .

 2. They reside on outer mitochondrial membrane and keep it impermeable.

 3. Thus , prevent cytochrome C and other death inducing protein from leakage .

This is possible only while anti Apoptotic is receiving Growth factor signals.

When there is withdrawal of growth factor , or DNA damage , or protein misfolding (ER stress) , then

 4. Pro- Apoptotic (BAX, BAK ) . They posses first three BH domain called BH1-3 .

 5. They increases the permeability of outer mitochondrial membrane

 6. Thus , cytochrome C and other death inducing protein leakage out into the cytoplasm.

 7. Cytochrome C combine with APAF-1 (Apoptosis activating factor-1 ) and forms a structure called apoptosome. these apoptosome activate pro-caspase 9 to caspase 9. Which is the initiator caspases.

  Now these initiator caspases activate executioner caspases. Executioner caspases digest cytoskeleton of the cytoplasm, supporting protein for nucleus, activate DNAase and help in DNA degradation. Then Apoptotic bodies is formed which is engulf by macrophages.

 8. Other death inducing protein such as Smac/DIABLO bind to and neutralize cytoplasmic protein which function as inhibitors of apoptosis (IAPs).