Apoptosis, or programmed cell death, occurs through two main pathways: the extrinsic pathway and the intrinsic pathway.
Extrinsic Pathway (Death Receptor Pathway)
The extrinsic pathway, also known as the death receptor pathway, is initiated by external signals. These signals bind to specific death receptors on the cell surface, triggering a cascade of events leading to cell death. This pathway is crucial for eliminating cells that are no longer needed or that pose a threat to the organism. Examples include immune cell-mediated elimination of infected or cancerous cells.
- Initiation: Begins with the binding of extracellular ligands (like FasL or TNF-α) to their corresponding death receptors (like Fas or TNFR1) on the cell membrane.
- Caspase Activation: This binding forms the death-inducing signaling complex (DISC), activating initiator caspases (like caspase-8 and caspase-10).
- Execution: Initiator caspases then activate executioner caspases, leading to the dismantling of the cell.
Intrinsic Pathway (Mitochondrial Pathway)
The intrinsic pathway, also called the mitochondrial pathway, is triggered by internal cellular stress. This stress can arise from various sources, such as DNA damage, lack of nutrients, or cellular injury. The pathway involves the mitochondria and a family of proteins called Bcl-2. This pathway regulates cell death in response to internal cellular damage or dysfunction.
- Initiation: Internal cellular stress leads to changes in the permeability of the mitochondrial membrane.
- Cytochrome c Release: This increased permeability releases cytochrome c into the cytoplasm.
- Apoptosome Formation: Cytochrome c binds to Apaf-1, forming the apoptosome, which activates caspase-9 (an initiator caspase).
- Execution: Caspase-9 subsequently activates executioner caspases, causing cell death.
Both pathways converge on the activation of executioner caspases, which are responsible for the dismantling and removal of the dying cell. While distinct in their initiation, both pathways ultimately lead to the same outcome: programmed cell death. Understanding these pathways is crucial in various fields, including cancer research and the development of new therapeutic strategies.
