Lecture 25 - Cell Death Flashcards
why do cells undergo apoptosis?
- embryonic development requires the elimination of excess cells
- cells that sustain irreparable genomic damage need to be removed
- removal of cells that aren’t useful anymore
failure to carry out apoptosis leads to…
cancer
overzealous apoptosis leads to…
diabetes
what characterizes apoptosis?
- overall shrinkage in volume of the cell and nucleus
- loss of adhesion to neighbouring cells
- formation of blebs on the cell surface
- fragmentation of the genome
what engulfed cell corpses through phagocytosis?
neutrophils or macrophages
def: less orderly form of cell death
necroptosis
what characterizes necroptosis?
- swelling of the cell and internal organelles
- membrane breakdown
- leakage of the cell contents into the extracellular space
- the induction of inflammation
why does necropolis usually happen?
when cells fail to undergo apoptosis following exposure to stressors
how can necroptosis be beneficial?
can lead to an inflammation response
apoptosis is like __________ ______________
necroptosis is like __________ _____________
controlled implosion
uncontrolled explosion
def: group of cysteine proteases that are responsible for triggering most of the changes during cell death
caspases
what do caspases cleave?
- cytoskeletal compnents, disrupting cell shape
- lamins, breaking down nucleus
- protein kinases, regulate cell adhesion
- DNase inhibitors, activate DNases that fragment genome
what is induction of the apoptotic triggered by?
- external (extrinsic pathway)
- internal (intrinsic pathway)
what is the death receptor on the extracellular side of the cell?
trimeric transmembrane TNF receptor protein
what does receptor ligand binding induce in the TNF receptor, in extrinsic apoptosis?
induces conformational change of the TNF receptor, leading to the recruitment of cytosolic proteins
what leads to trans-autocleavage within the cell?
clustering of procaspases upon recruitment to membrane-bound (early) and cytosolic (late) complexes
how does procaspase-8 become active/inactive?
inactive with pro region
active without pro region
cascade-8 is an ___________ caspase that activates _________ caspases, which carry out the destruct of the cell
initiator, executioner
what do internal signals for intrinsic cell death activate within the cells?
the Bcl-2 family of proteins, which can target Bax to the mitochondrial membrane
what happens to Bax when it is target to the mitochondrial membrane?
undergoes a conformational change, which allows it to form a multi-subunit membrane channel in the outer mitochondrial membrane
what resides in the inter membrane space and is released into the cytosol upon Bax forming a channel in the outer mitochondrial membrane?
cytochrome c
what does cytochrome C do ?
forms a wheel-shaped complex, called an apoptosome, which brings together procaspase-9
T or F: initiation of procaspase-9 does not require proteolytic cleavage, activated simply by joining the apoptosome
true
in necroptosis, what is not activated?
caspase-8
what happens in the necrosome?
series of interactions result in oligomerization an activation of RIP1K and RIP3K
what does kinase RIP3K activate?
MLKL which gets targeted to the plasma membrane after it is phosphorylated
what does MLKL do?
scrambles the phospholipids, causing the membrane to lose integrity and the cell dies
