Apoptosis, or programmed cell death, occurs through two primary pathways: the extrinsic and intrinsic pathways. These pathways, while distinct, share some overlapping components and ultimately lead to the controlled demolition of a cell.
1. Extrinsic Pathway (Death Receptor Pathway)
The extrinsic pathway is initiated by external signals. Specifically, it begins when death ligands, such as Fas ligand (FasL) or TNF-α, bind to their respective death receptors (e.g., Fas or TNFR1) on the cell surface. This binding triggers a cascade of events involving adaptor proteins (like FADD) and initiator caspases (like caspase-8), leading to the activation of executioner caspases (like caspase-3 and caspase-7). These executioner caspases then dismantle the cell's internal structure, causing its demise.
- Initiation: Binding of death ligands to death receptors on the cell membrane.
- Signaling Cascade: Activation of initiator caspases via adaptor proteins.
- Execution: Activation of executioner caspases, leading to cell disassembly.
2. Intrinsic Pathway (Mitochondrial Pathway)
The intrinsic pathway is triggered by internal cellular stress, such as DNA damage, oxidative stress, or lack of growth factors. This stress activates pro-apoptotic proteins from the Bcl-2 family (like Bax and Bak), which permeabilize the mitochondrial membrane. This release of cytochrome c into the cytoplasm then leads to the formation of the apoptosome, a complex that activates initiator caspase-9. Similar to the extrinsic pathway, this subsequently activates executioner caspases resulting in apoptosis.
- Stress Signal: Internal cellular stress activates pro-apoptotic proteins.
- Mitochondrial Disruption: Release of cytochrome c from mitochondria.
- Apoptosome Formation: Formation of the apoptosome complex and activation of caspase-9.
- Execution: Activation of executioner caspases, leading to cell disassembly.
Both pathways converge on the activation of executioner caspases, the ultimate effectors of apoptosis. While distinct in their initiation, these two pathways represent the fundamental mechanisms of programmed cell death. Understanding these pathways is crucial for comprehending various biological processes and disease mechanisms.
