Question

Which of the following statements is not true about intrinsic pathway of apoptosis:

a) Cytochrome c release into the cytosol leads to METC uncoupling and superoxide production

b) Activation of death receptors by ligands

c) Activates initiator and executioner caspases

d) Involves cytochrome c release after oxidative insult

e) Apoptosome could induce caspase-9 dimerization

Answer 1

The intrinsic pathway of apoptosis

Intrinsic pathway of apoptosis is a response to injury or other stresses, for eg., DNA damage or lack of oxygen. Intracellular activation of apoptotic death depends on release of Cytochrome C (mitochondria) into cytosol. The steps involved are:

1. Release of cytochrome C from mitochondria to cytosol of the cell.

2. Cytochrome C binds to procaspase called Apaf1(apoptotic protease activating factor-1) and hydrolyse dATP to dADP, this induces Apaf1 and cytochrome c to aggregate to form apoptosome it to oligomerize and form a complex called apoptosome (it's a wheel -like heptamer).

3. The Apaf1 proteins in the apoptosome recruits initiator procaspase proteins (procaspase-9), through CARD (caspase
recruitment domain) domain which are activated by proximity in the apoptosome.

4.The activated caspase-9 molecules cleaves and activates downstream executioner procaspases, which leads to the cleavage and activation of molecules in a caspase cascade.

Activation of death receptors by ligands happens in Extrinsic pathway of apoptosis, not in Intrinsic pathway of apoptosis