1. Activation of Caspases:
* Caspases are a family of cysteine proteases that play a central role in apoptosis.
* They are initially present as inactive pro-caspases and are activated through a cascade of proteolytic cleavages.
* The activation of initiator caspases (like caspase-8 and caspase-9) triggers the activation of executioner caspases (like caspase-3, -6, and -7).
2. DNA Fragmentation:
* Activated caspases cleave nuclear proteins, including DNA-associated proteins like lamins and histone proteins.
* This results in the breakdown of DNA into fragments of specific sizes (multiples of 180-200 base pairs) which can be detected by gel electrophoresis.
3. Cell Shrinkage:
* The cell shrinks in size due to the breakdown of cytoskeletal proteins and loss of water.
* This process also involves changes in the plasma membrane, such as blebbing (formation of small, round protuberances).
4. Formation of Apoptotic Bodies:
* As the cell shrinks, the cytoplasm and nucleus fragment into smaller, membrane-bound vesicles called apoptotic bodies.
* These bodies contain cellular components like organelles, DNA fragments, and cytosol.
5. Phagocytosis by Neighboring Cells:
* Apoptotic bodies are quickly engulfed and digested by neighboring cells, such as macrophages, preventing the release of potentially harmful cellular contents into the extracellular space.
6. Cell Signaling:
* Apoptosis is triggered by a variety of signals, including:
* Intrinsic pathways: These are triggered by internal stress signals like DNA damage, growth factor deprivation, or reactive oxygen species (ROS).
* Extrinsic pathways: These are triggered by external signals such as death ligands (like TNF-alpha and Fas ligand) that bind to cell surface receptors.
7. Mitochondrial Involvement:
* Mitochondria play a critical role in apoptosis by releasing pro-apoptotic proteins (like cytochrome c) into the cytoplasm.
* This release triggers the activation of caspase-9 and the downstream apoptotic cascade.
Overall, apoptosis is a highly orchestrated process that ensures the orderly dismantling of a cell without causing inflammation or damaging surrounding cells.
