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Difference Between Intrinsic and Extrinsic Pathway of Apoptosis

  • Post last modified:April 4, 2023
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Brief overview of Intrinsic and Extrinsic Pathway of Apoptosis

Apoptosis, also known as programmed cell death, is a natural process of cell death that occurs in the body. There are two main pathways of apoptosis: intrinsic and extrinsic.

The intrinsic pathway of apoptosis is activated by cellular stress, such as DNA damage or cellular damage. This pathway involves the release of proteins from the mitochondria, which then activate caspases, a type of enzyme that cleaves other proteins and leads to cell death.

The extrinsic pathway of apoptosis, on the other hand, is activated by external signals, such as the binding of specific ligands to death receptors on the cell surface. This pathway involves the activation of caspases through a signaling cascade, ultimately leading to cell death.

While both pathways ultimately lead to apoptosis, they differ in their source of signal for activation, the timeframe of activation, and key players and mechanisms involved. Understanding these differences is important in the study of apoptosis and its role in various physiological processes.

Intrinsic Pathway of Apoptosis

The intrinsic pathway of apoptosis, also known as the mitochondrial pathway, is activated by internal cellular stress, such as DNA damage or cellular damage. This pathway is controlled by the Bcl-2 family of proteins, which regulate the permeability of the mitochondrial outer membrane.

When a cell receives a signal to undergo apoptosis, pro-apoptotic Bcl-2 family proteins, such as Bax and Bak, are activated and translocate to the outer mitochondrial membrane. This results in the release of mitochondrial intermembrane proteins, including cytochrome c, which activates the caspase cascade.

Caspases are a type of protease enzyme that cleave specific target proteins and ultimately leads to the breakdown of the cell. Caspases are activated by the formation of the apoptosome, a complex composed of cytochrome c, Apaf-1, and procaspase-9.

The intrinsic pathway of apoptosis is important for removing cells that are damaged or no longer needed by the body. Dysregulation of this pathway has been implicated in various diseases, such as cancer and neurodegenerative disorders.

Extrinsic Pathway of Apoptosis

The extrinsic pathway of apoptosis, also known as the death receptor pathway, is activated by external signals that bind to death receptors on the cell surface. These signals are typically cytokines, such as tumor necrosis factor (TNF) or Fas ligand (FasL).

When a death ligand binds to its corresponding death receptor, it causes the formation of a death-inducing signaling complex (DISC) composed of Fas-associated death domain (FADD) and procaspase-8. Procaspase-8 is then activated and cleaves downstream caspases, ultimately leading to cell death.

In some cases, the extrinsic pathway of apoptosis can also activate the intrinsic pathway. This occurs when caspase-8 cleaves and activates the pro-apoptotic Bcl-2 family protein Bid, which translocates to the mitochondria and triggers the release of cytochrome c.

The extrinsic pathway of apoptosis plays an important role in immune responses and development, as well as in the elimination of cells that are infected or damaged. Dysregulation of this pathway has been implicated in various diseases, such as autoimmune disorders and cancer.

Differences between Intrinsic and Extrinsic Pathway of Apoptosis

The intrinsic and extrinsic pathways of apoptosis differ in several ways:

  1. Source of signal for activation: The intrinsic pathway is activated by internal cellular stress, such as DNA damage or cellular damage, whereas the extrinsic pathway is activated by external signals, such as binding of specific ligands to death receptors on the cell surface.
  2. Timeframe of activation: The intrinsic pathway can be activated slowly over a period of time, whereas the extrinsic pathway is activated rapidly in response to an external signal.
  3. Key players and mechanisms involved: The intrinsic pathway is controlled by the Bcl-2 family of proteins, which regulate the permeability of the mitochondrial outer membrane, and involves the release of mitochondrial intermembrane proteins, including cytochrome c, which activates the caspase cascade. The extrinsic pathway is controlled by death receptors on the cell surface and involves the formation of a DISC complex, which activates caspases.
  4. Function and role in the body: The intrinsic pathway is involved in removing cells that are damaged or no longer needed by the body, whereas the extrinsic pathway plays an important role in immune responses and development, as well as in the elimination of cells that are infected or damaged.

While both pathways ultimately lead to apoptosis, they differ in their source of signal for activation, timeframe of activation, and key players and mechanisms involved. Understanding these differences is important in the study of apoptosis and its role in various physiological processes.

Conclusion

Apoptosis is a natural process of cell death that occurs in the body and is essential for maintaining tissue homeostasis. The intrinsic and extrinsic pathways of apoptosis are two main mechanisms by which cells undergo programmed cell death.

The intrinsic pathway is activated by internal cellular stress, while the extrinsic pathway is activated by external signals.Both pathways involve the activation of caspases, but differ in their key players and mechanisms involved, timeframe of activation, and function in the body.

Understanding the differences between the