Apoptosis Flashcards
Why do metazons need apoptosis?
3
1- need a body plan that requires tissue shaping,
2- eliminate infected cells,
3- eliminate cells that do not retain genomic integrity
Why and when is apoptosis needed?
4
1- During development.
Sculpting structures e.g. digits.
2- During immune system shaping.
Eliminating self-reacting cells.
3- Deleting damaged cells
Virus infected cells.
Sunburn, Radiation.
Genetic abnormality.
4- Eliminating misplaced cells
Cancer.
Autoproliferative disorders
among survival and apoptosis what is the default pathway and why
Apoptosis is the default pathway.
Cells require signals in the form of cell-cell contacts, cell-substrate contact and soluble factors (growth factors) to live.
Cell death is classified according to what 4 criteria
1- Its regulation (regulated vs non-regulated).
2- Its function.
3- Morphological changes.
4- Biochemical changes.
Breifly describe the intrinsic apoptotic pathway
- Dna damage
- P53 is activated
- Bax makes a hole in the mitochondria (which depolarises it)
- Contents leak out (Cytochrome C, SMAC, Diablo and calcium)
- Activates caspase 9 (initiator caspase)
- Activating enzymes caspase 6 3 and 7 (effector caspases)
- Cleave important proteins in cell- lamin, I/CAD, PARP
- Leading to DNA fragmentation protein cleavage nuclear fragmentation and organelle breakdown – which causes cell death
Breifly describe the two extrinisic apoptopic pathways
Type 1 extrinsic pathway -
1. extrinsic stimuli
2. death receptor activation triggers caspase 8
3. links to the the effector caspases 3, 6 & 7
4. these cleave important proteins (ICAD PARP Lamin) in the cell
5. DNA fragmentation. protein cleavage, nuclear membrane loss and organelle breakdown lead to cell death
Type 2 extrinsic pathway - the same until caspase 8, which makes tBid which acts upon mitochondrion to create holes. resulting in depolarisation of the organelle and leaking of its contents then activation of effector caspases and cell death (fastest pathway)
In apoptosis when is the point of no return
the depolarisation and leaking of mitochondrial contents
(downstream/loss of MMP)
because it cant make ATP anymore
MMP - mitochondrial membrane polarisation
What are caspases and how are they activated?
Caspases (cystein aspartic proteases): core of apoptotic pathways
They are calcium dependent proteases
Activation of caspases: proteolytic cleavage of procaspases
What is the structure of an active caspase
Made out of small and large subunits which associate in heterodimers and comes together in a heterotetramer
what are the two types of caspases and how do they work together to ensure cell death?
Initiator and effector caspases
Initiator caspases activated effector caspases by cleaving their procaspases, then the effector caspases cleave initiator procaspases to activate more of them in a feedback amplification loop
in the extrinsic pathway, initiator caspases require what for activation
what is the complex called?
initiator caspases require a platform and proximity activation
The DISC (death inducing signal complex) (a multiprotein complex)
what are the components of the DISC multiprotein complex
and what is its function
Fas ligand and receptor (trigger)
FADD (adaptor)
Pro-caspase 8
It activates caspase 8 in the extrinsic apoptotic pathway - Fas ligand an receptor brought in proximity and bind, which brings in FADD adaptor which recruits two procaspases. These two procaspases cleave each others bottom and bind creating an active caspase 8
What proteins are a part of the wheel of death?
aka apoptosome
cytochrome c, APAF-1, WD40, CARD
(times 7)
what is the key event in the initiation of apoptosis?
the release of mitochondrial contents to cytoplasm such as calcium and cytochrome c
how does bax induce apoptosis?
Bax induces apoptosis by forming pores in the mitochondrial membrane
BH3 proteins come together to make a funnel and insert themselves into the mitochondrial membrane so that mitochondrial contents go out of the organelle, eg calcium cyto c
