Question

intrinsic and extrinsic apoptosis

Answer 1

Apoptosis is programmed cell death, a process in which damaged or unwanted cells is removed in a programmed fashion. It involves cellular changes like chromosomal fragmentation, chromatin condensation, nuclear breakage, blubbing and cell breaking into apoptotic bodies.

Apoptosis occurs via two different pathways

The extrinsic or the death receptor pathway (signal comes from outside the cell)

and the intrinsic or the mitochondrial pathway (signal comes from within the cell)

Both of these pathways differ in the initiation phase of apoptosis but are similar in the execution phase. The purpose of both the pathways is to activate caspases- family of protease enzymes which execute the programmed cell death.

Extrinsic pathway

Fas receptor is found in the cell membrane which has fas associated death domain in its cytoplasmic side and the fas ligand bound to this receptor will activate the death domain (DD) of the receptor. DD then will activate DISC or death inducible signaling complex. DISC will cleave and activate initiator pro caspase 8 into caspase 8. Caspase 8 is an initiator caspase. Caspase 8 will cleave and activate other procaspase 8 molecules and caspase 8 molecules will cleave and activate effecter caspases- 3 and 6 which will carry out the apoptotic process, by causing degradation of chromosome and cytoskeletal proteins.

Intrinsic pathway

Due to intracellular signals (from within the cells) the proapoptotic (causes apoptosis) proteins like Bid and Bad are activated and they block the function of anti apoptotic (prevents apoptosis) proteins like Bcl-2 and Bcl-x. Other proapoptotic proteins like Bax and Bak are activated and these proteins will create pores in the mitochondrial membrane. This causes cytochrome C to leak from mitochondria into cytoplasm. Cytochrome C there will bind with APAf-1 protein (apoptosis activating factor-1) to form apoptosome complex. Apoptosome will cleave and activate procaspase 9 into caspase 9 which is an initiator caspase. Caspase 9 will cleave and activate other procaspase 9 molecules and activated caspase 9 molecules will cleave and activate effector caspases like caspase 3 and caspase 6 which in turn will execute the apoptotic process.