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What is In apoptosis, Apaf-1 is activated by release of which of the following substances from the mitochondria? and explain in detail?
The integrity of the mitochondrial outer membrane is regulated by pro-apoptotic and anti-apoptotic members of the BCL2 family of proteins. The pro-apoptotic proteins BAX and BAK are directly promoting mitochondrial permeabilization. Their action is inhibited by the anti-apoptotic proteins BCL2 and BCL-XL. The third set of proteins, the so-called BH3-only proteins, which include BAD, BID, and PUMA, regulate the balance between the pro- and anti-apoptotic members of the BCL2 family.The BH3-only proteins promote apoptosis by neutralizing the actions of anti-apoptotic proteins like BCL2 and BCL-XL. When the sum total of all BH3 proteins expressed "overwhelms" the anti-apoptotic BCL2/ BCLXL protein barrier, BAX and BAK are activated and form pores in the mitochondrial membrane. Cytochrome c leaks into the cytosol, where it binds to APAF-1 and activates caspase-9. Like caspase-8 of the extrinsic pathway, caspase-9 can cleave and activate the executioner caspases. ( Robbins Basic Pathology, 9th edition, page 189 )