Apoptosis, or programmed cell death, is achieved through two primary pathways: the extrinsic pathway and the intrinsic pathway.
Apoptosis Pathways
Apoptosis is a fundamental process vital for maintaining cellular homeostasis and preventing the proliferation of damaged cells. These pathways ensure that cells die in a controlled and orderly manner, avoiding inflammation and harm to surrounding tissues.
Pathway | Initiating Factors | Primary Agents | Mechanism |
---|---|---|---|
Extrinsic Pathway | Signals from cytotoxic T cells of the immune system | Death receptor ligands (e.g., Fas ligand, TNF) | Activated death receptors trigger a cascade of caspases, leading to cell dismantling. |
Intrinsic Pathway | DNA damage, loss of mitochondrial membrane potential | Cytochrome c release from mitochondria, cellular stress signals | Cytochrome c activates caspases via apoptosome formation, resulting in cell death. |
Extrinsic Pathway
The extrinsic pathway is triggered by external signals, primarily by cytotoxic T cells of the immune system.
- Immune System Involvement: Cytotoxic T cells recognize and bind to target cells, such as virus-infected cells or tumor cells.
- Death Receptor Activation: This binding initiates a signaling cascade through death receptors, like Fas or TNF receptors, located on the cell surface.
- Caspase Activation: Once death receptors are activated, they activate initiator caspases (e.g., caspase-8), which then activate executioner caspases.
- Cellular Dismantling: These caspases dismantle cellular components, leading to the controlled death of the cell.
Intrinsic Pathway
The intrinsic pathway, also known as the mitochondrial pathway, is initiated by internal cellular stressors.
- Internal Stress: Factors like DNA damage, lack of growth factors, or loss of mitochondrial membrane potential can initiate this pathway.
- Mitochondrial Involvement: Damaged mitochondria release cytochrome c into the cytoplasm.
- Apoptosome Formation: Cytochrome c forms a complex called the apoptosome with other proteins.
- Caspase Cascade: The apoptosome activates caspase-9, which then activates executioner caspases, resulting in cell death.
- Cellular Self-Destruction: These activated caspases initiate the process of cellular dismantling, leading to apoptosis.
In summary, apoptosis is achieved through two distinct pathways:
- The extrinsic pathway which is triggered by external signals from immune cells that lead to the activation of caspases through death receptors.
- The intrinsic pathway which is activated by internal cellular stress and damages, which leads to the release of cytochrome c from mitochondria and activation of caspases, resulting in cell death.