APOPTOSIS AND NECROSIS Flashcards
What is the importance of apoptosis?
1- embryo development - sculpting tissue
2- immune system - destroys self reacting immune cells to ensure they don’t do further damage, and destroys virus infected cells (tells them to self destruct)
3. Homeostasis - counterbalance to cell division and removal of old and dead cells
4. cancer - most cancer treatments work by inducing apoptosis
How is apoptosis triggered? what do they do?
2 pathways
- receptor mediated (extrinsic)
- mitochondria mediated (intrinsic)
these induce apoptosis by activating a class of proteases in the cell called caspases
what are caspases
cysteine aspartic proteases - following activation by cleavage, they can activate other caspases in a cascade
activation of caspases is the point of no return in apoptosis
what are the 2 types of apoptotic caspases
initiator caspases - activate other caspases
Effector (executioner) caspases - break down cellular components and DNA
define apoptosis
programme cell death that is regulated and controlled - essential for health and development
define necrosis
uncontrolled cell death - associated with disease
what role does plasma membrane play in apoptosis
there is a flip over of phosphatidyl serine from the inner layer to the outer layer - this acts as an eat me signal for macrophages which destroy apoptotic cell - phagocytosis
what is the role of mitochondria in apoptosis
cytochrome C is in the IMM - in the intrinsic pathway- pores form in the outer mitochondrial membrane allowing the release of cytochrome C into cytosol - this triggers apoptosis.
- Cytochrome C binds to other cytosolic proteins to form a multi protein complex called an apoptosome
what does formation of an apoptosome require?
cytochrome C
Apaf-1 protein
pro-caspase 9
ATP
what happens with the apoptosome?
End result Is cleavage and thus activation of pro-caspase 9 into active cassias 9 - an initiator cascade
what is the role of the bcl-2 family of proteins?
responsible for the regulation of cytochrome C release from the mitochondria
what does the bcl-2 family of proteins ability to induce apoptosis depend on?
the balance between its anti-apoptotic members and pro-apoptotic members
what are the anti-apoptotic members of bcl-2?
exist on OMM - act to block action of the pro-apoptotic members
What are the pro apoptotic members of bcl-2?
work by inserting themselves into the mitochondrial surface & promote formation of large pores in outer membrane that leads to release of cytochrome C
what are the features of necrosis
- unregulated
- driven by extrinsic factors
- Caspase independent process
