Answer in detail.

Solution:

Apoptosis or programmed cell death is a mechanism exhibited by cells of multicellular organisms which controls the division of cells as an uncontrolled cell division causes a tumor or cancer. Apoptosis pathway can be induced by various means. After induction, there comes early phase, mid phase, and late phase. The pathway could be either intrinsic or extrinsic. Given below is the description of intrinsic pathway of apoptotic cell death.

Intrinsic pathway- This is induced in response to pro-apoptotic stimuli such as DNA damage which could be due to UV light, osmotic stress, etc.

Early phase- After getting stimuli, the B-cell Lymphoma 2 (Bcl-2) family signaling cascades gets activated. The members of the Bcl- family (PUMA, Bcl-2-associated agonist of cell death (Bad) and NOXA) gets activated by DNA damage. This leads to inhibition of the anti-apoptotic members Bcl-2. Now, Bcl-2 homologous antagonist killer (BAK) and Bcl-2-associated x protein (BAX) easily insert themselves into the mitochondrial membrane.

Mid phase- In the mid stage, there is loss of mitochondrial membrane integrity. This event commits the cell irreversibly to apoptosis. Cytochrome c is released from the disintegrated mitochondria along with other proteins such as APAF-1. In the cytoplasm, cytochrome c, APAF-1 and pro-caspase-9 form the apoptosome leading to activation of caspase-9. This Caspase-9 activationin turn activate effector caspases.

Late phase- At this phase of apoptosis, the extrinsic and intrinsic pathways converges and caspase-3/7 gets activated. This results in DNA fragmentation and cell membrane disruption.This phase is characterized morphologically by shrinking of cell and phagocytosis of the apoptotic cell by macrophages.

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