Apoptosis – a molecular series of cell death

Apoptosis is a planned cell death process. In which the regulation of cell degeneration is controlled by the molecular series of genes. On the gene level cells regulate the process and form a gene series of apoptosis. In apoptosis Cell shrinking occurs, DNA fragments formation, Chromatin condensation, and apoptotic cell body formation occur. The best examples are c.elegan and higher animals for this apoptosis process.

Apoptotic Cells & gene:

All cells are growing within particular stages in their lifecycle. Cells divide, grow and die in their life span. In apoptosis different cell stages like pre-apoptotic, anti-apoptotic, and late apoptotic are for the regulation of all cell stages. Regulation is controlled by their regulative genes. There is a gain of function and loss of function present in gene regulation. There are multiple genes associated with the regulation of apoptosis and they are closely related to each other. If apoptosis will suppress then cancer occurs in the body.

Apoptosis process in C. elegans:

Regulation of Apoptosis:

• CED-9 gene is an anti-apoptotic gene, which suppressed and holds the CED-4, an apoptotic gene to prevent the activation of the apoptosis process. 
• EGL-1 is a pro-apoptotic gene which suppressed and holds the CED-9 gene to suppress the effect of the anti-apoptotic gene on apoptosis.
• CED-4 is an adaptor protein also which activates the CED-3 which is an executive caspase.
• CED-3 activates and executes the apoptosis process.

Gain of function:

• If EgL-1 gains function that means it is suppressed by the CED-9 to activate the process of apoptosis.
• If CED-9 gain function then the apoptosis process become held and suppressed.
• If CED-4 gains function than CED-3 would be activated and it make apoptosis. 

Loss of function:

• If Egl-1 is in loss of function then it cannot induce apoptosis.
• If CED-9 is in loss of function then the apoptosis process started.
• If CED-4 is in loss of function then it could not activate the CED-3 gene.
• If CED-3 is in loss of function then apoptosis is not complete.

Apoptosis in Humans:

Regulation of Apoptosis:

• BCL-2 gene is an anti-apoptotic gene, which suppressed and holds the BAK/BAx an apoptotic gene to prevent the activation of the apoptosis process. 
• BH3 is a pro-apoptotic gene which suppressed and holds the BCL-2/ BCL-XL gene to suppress the effect of the anti-apoptotic gene on apoptosis.
• BAK/BAX is an adaptor protein also which activates the APAF-1 which is an executive caspase, it begins the process.
• APAF-1 activates caspase-9 to activate caspase-3.
• Caspase-9 activates and executes the process of apoptosis process.

Gain of function:

• If BH3 gains function that means it is suppressed by the BCL-2 /BCL-XL to activate the process of apoptosis.
• If BCL-2/ BCL-Xl gain function then the apoptosis process becomes held and suppressed.
• If BAK/BAX gain function then caspase-9 and caspase-3 would be activated and make the apoptosis process begin. 

Loss of function:

• If BH3 is in loss of function then it cannot induce apoptosis.
• If BCL-2/BCL-XL is in loss of function then the apoptosis process starts.
• If BAK/BAX is in loss of function then it could not activate the APAF-1 gene.
• If caspase-9 and caspase-3 lose of function then apoptosis is not complete.

The extrinsic pathway of Apoptosis:

In the extrinsic pathway of apoptosis, there is an example of the virus, which enters the body to infect a human cell or a cancer-transformed cell. In this pathway, an FAs ligand attaches to the death Receptor. The receptor domain detached from the cell surface. A proteolytic cleavage occurs in between the path effecter domain and receptor domain.

Pro-caspase- 8, 10 activate and initiates the process of apoptosis so it is called initiator caspase. Caspase-8, 10 activate the caspase-3 that is an Executioner caspase. Caspase-3 activates and completes or executes the apoptosis.

                          Extrinsic Pathway of apoptosis

The intrinsic pathway of Apoptosis:

If an apoptotic cell stimulates mitochondria then in this pathway the apoptosis process occurs. On the mitochondrial cell surface, the intrinsic pathway begins. BAK/BAX activates APAF-1 to stimulate caspase-9 gain of function. Caspase-9 gain of function makes caspase-3 activated. Caspase-3 completed apoptosis.

Intrinsic Pathway of apoptosis

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