20210646 ‫خالد طارق مودد‬

Discuss in details the mechanism of apoptosis

The mechanism of apoptosis involves a series of intricate molecular events that culminate in the
.orderly dismantling and removal of the cell without causing inflammation

Apoptosis can be triggered by various intrinsic and extrinsic signals, including DNA damage,
cellular stress, growth factor deprivation, and activation of death receptors on the cell surface.
Regardless of the initiating signal, the execution of apoptosis involves two main pathways: the
intrinsic pathway (also known as the mitochondrial pathway) and the extrinsic pathway (also
.known as the death receptor pathway)
:Intrinsic Pathway .1
The intrinsic pathway is primarily regulated by the balance between pro-apoptotic proteins, such
as Bax and Bak, and anti-apoptotic proteins, such as Bcl-2 and Bcl-xL, which are located in the
mitochondria. When cells receive stress signals, such as DNA damage or growth factor deprivation,
pro-apoptotic proteins are activated, causing mitochondrial outer membrane permeabilization
.(MOMP)
:Cytochrome c Release .2
The released cytochrome c in the cytoplasm forms a complex with Apaf-1 (apoptotic protease
activating factor 1) and procaspase-9, which is known as the apoptosome. This complex activates
.procaspase-9, initiating a caspase cascade

:Caspase Cascade .3
Caspases are a family of proteases that play a central role in apoptosis. Activation of caspase-9
leads to the activation of downstream effector caspases, such as caspase-3, -6, and -7. Effector
caspases cleave a wide range of cellular substrates, including structural proteins, DNA repair
.enzymes, and inhibitors of DNase, ultimately resulting in cellular disassembly

:Extrinsic Pathway .4
The extrinsic pathway is initiated by the binding of extracellular death ligands, such as Fas ligand
(FasL) or tumor necrosis factor-alpha (TNF-α), to death receptors on the cell surface, including Fas
(CD95) and TNF receptor 1 (TNFR1). This binding leads to the recruitment and activation of
.initiator caspases, such as caspase-8 and -10, at the receptor complex

:Death Receptor Activation .5

Activated caspase-8 or -10 can directly cleave and activate downstream effector caspases, such as
.caspase-3, -6, and -7, initiating the caspase cascade similar to the intrinsic pathway

:Convergence of Intrinsic and Extrinsic Pathways .6

The intrinsic and extrinsic pathways are interconnected at multiple levels. For example, caspase-8,
activated by the extrinsic pathway, can cleave Bid (a pro-apoptotic protein), generating a
truncated form called tBid. tBid then translocates to the mitochondria and promotes MOMP,
.triggering the release of cytochrome c and activation of the intrinsic pathway

:Execution Phase .7
The activated effector caspases cleave various cellular substrates, leading to characteristic
apoptotic changes, such as nuclear condensation, DNA fragmentation, membrane blebbing, and
formation of apoptotic bodies. These changes facilitate the removal of dying cells by phagocytes,
minimizing inflammation