12.3. Cell Death Flashcards
Apoptosis…
A programmed form of cell death, resulting from an active decision by the cell to undergo death.
Mechanism of apoptosis…
(5 stages)…
The cell condenses and membrane blebs (but remains intact).
The nucleus shrinks and chromatin condenses and fragments.
Apoptotic bodies form.
DNA and proteins are broken down (autodigestion of cellular components).
The dying cell is recognised by phagocytes and is engulfed (endocytosis). No immune response is triggered as cell contents are not released.
The importance of apoptosis…
To regulate the number of cells, to balance cell division.
To sculpt the body (fingers in humans, the whole body in frogs).
To ensure immunity:
- Removes immune cells after an immune response to bring levels back down to normal again.
- Removes lymphocytes that have auto-immune tendencies.
- Removes cells infected with viruses (cytotoxic T cells).
- Removes cells with DNA damage, to prevent tumours.
Caspase summary…
Cysteine proteases, found in the cytoplasm and mitochondria in inactive forms, are inhibited by IAP proteins.
They need to be cleaved to become active.
They are cleaved after an aspartic acid residue.
Classes of caspases…
Initiator caspases (8, 9, 10):
- Activated by pro-apoptotic stimuli.
- Cleave and activate executor caspases.
Executor caspases (3, 6, 7):
- Activated by initiator caspases.
- Cleave a variety of target proteins resulting in the execution of apoptosis, including cytoskeletal and nuclear proteins.
Death receptor pathway…
A ligand binds to a death receptor.
The death receptor undergoes trimerisation, in which procaspase-8 and procaspase-10 are recruited and form dimers.
They cleave themselves which activates caspase 8 and caspase 10.
They then cleave executor caspases 3, 6 and 7.
Intrinsic pathway…
A large complex forms inside the cells of procaspase-9.
This binds with Apaf1 and cytochrome C, to form the apoptosome.
This procaspase-homodimer cleaves itself to form an active caspase-9.
Caspase-9 then cleaves executor caspases 3, 6 and 7.
Regulation of the intrinsic pathway…
Cytochrome C, usually held in the intermembrane space in the mitochondria, triggers the formation of the apoptosome.
The release is triggered by the opening of pores in the mitochondrial outer membrane.
This is regulated by Bcl-2 proteins, a protein that antagonises pore formation. The cell must overcome this to activate programmed cell death.
Necrosis…
A passive form of cell death, resulting from damage to the cell, such as extreme temperatures, low oxygen or nutrient starvation.
Mechanism of necrosis…
The cell swells.
This ruptures the cell membrane (cell lysis) causing the contents to spill out.
The lysis of the cell generates an immune response, which may trigger necrosis in neighbouring cells.
Programmed types of cell death…
Apoptosis.
Autophagy.
Necroptosis.
Unprogrammed types of cell death…
Necrosis.
