What is the Difference Between Intrinsic and Extrinsic Pathway of Apoptosis?
🆚 Go to Comparative Table 🆚The intrinsic and extrinsic pathways of apoptosis are both naturally occurring processes by which a cell undergoes programmed cell death. The main difference between the two pathways lies in the origin of the signals that initiate the apoptotic process:
- Intrinsic Pathway: This pathway is initiated from within the cell, often in response to cellular stressors such as DNA damage, hypoxia, or oncogenes. The process begins when an injury occurs within the cell, and the resulting stress activates the apoptotic pathway. Key players in the intrinsic pathway include the mitochondrial outer membrane permeabilization (MOMP) and the regulation of pro-apoptotic and anti-apoptotic proteins.
- Extrinsic Pathway: This pathway is initiated by external signals from other cells or the extracellular environment, such as death receptors like Fas or TNF. The extrinsic pathway is mediated by death receptors belonging to the tumor necrosis factor (TNF) superfamily, including TNFR1, CD95/Fas, TRAIL-R1/DR4, and TRAIL-R2/DR5. Activation of these death receptors leads to the assembly of the death-inducing signaling complex (DISC), which ultimately triggers the apoptotic process.
Both the intrinsic and extrinsic pathways of apoptosis lead to the activation of a family of proteases, the caspases, which are responsible for the final cell demise in the execution phase of apoptosis.
Comparative Table: Intrinsic vs Extrinsic Pathway of Apoptosis
The intrinsic and extrinsic pathways of apoptosis are both naturally occurring processes by which a cell is directed to programmed cell death. Here is a table summarizing the differences between the two pathways:
| Intrinsic Pathway | Extrinsic Pathway |
|---|---|
| Begins when an injury occurs within the cell, such as oncogenes, direct DNA damage, hypoxia, or survival factor deprivation | Begins when conditions in the extracellular environment determine that a cell must die |
| Triggered by intrinsic stresses | Triggered by external environmental signals, such as gamma and treatment with cytotoxic drugs like actinomycin D, and removal of cytokines |
| Involves the Bcl-2 protein family, mitochondrial permeability, and apoptosome formation | Involves death receptors, death-inducing signaling complex, and caspase activation |
| Activates the caspase cascade at some point, resulting in apoptosis | Activates the caspase cascade at some point, resulting in apoptosis |
Both pathways eventually lead to the activation of a family of Cys (Cysteine) proteases, named caspases, that act in a proteolytic cascade to dismantle and remove the dying cell.
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