mitochrondria: cell death Flashcards
what is apoptosis>
programmed cell death
what is necrosis?
uncontrolled cell death
cells swell up and burst contents
what is necrosis assocated with?
disease
what causes necrosis
cells encounter toxin and then burst releasing this to neighbouring cells
what happens during necrosis?
lose membrane integrity/ control of membrane cell swells cytoplasm dilutes, slow reactions cells lyse loss of cell components inflammation endosomes and lysosomes released DNA degraded
what happens during apoptosis
membrane blebbs but remains in control
cells still viable
careful breakdown of nucleus and components
cell is packaged into small vesicles and contained
what happens to apoptosis fragements?
macrophages can digest the small fragments
how is cell death key in embryo development
it sculpts the tissue
eg. digit making
how is cell death used in the immune system ?
destroys self reacting cells
stops autoimmune issues
destroys virus infected cells
how is cell death used in homeostasis?
counter balance cell division and removal of old or damaged cells
replace with new instead of repearing
how is cell death used in cancer?
radiothereapy drugs work through inducing apoptosis
many cancer cells have defects in apoptosis pathway making them reistant
what are the two ways apoptosis is triggered?
receptor mediated
mitochondrai mediated
how does the receptor mediated pathway work>
recieve correct ligand and this triggers the death pathway
it is extrincically controlled
how does the mitochondrai control cell death?
intrisinic pathway
can be activated by variety of cell stresse
which cell stresses can lead to mitochondrial acttivated cell death?
free radicals DNA damage viral infection membrane damage loss of survival signals
what are caspases?
family of proteases existing in an inactive form of pro-enzymes in cells
how many caspases are there??
12
what do caspases do?
activate other caspases in a cascade.
how do caspases work in activating other caspases?
they cleave the pro-domain and activae the caspase to work
two types of caspases?
initiator
effector
what does an initiator caspase do?
activated other caspases
single caspase can activate lots of others in the cell
what does an affector caspase do?
called executeres
they break down cellular components such as the cytoskeleton and DNA
activation of these is the point of no return in process of apoptosis
how is the plasma membrane involved in cell death
key lipids are made on the inside and the membrane can flip over to reveal this
what causes the membrane to flip over?
caspases
when the membran flips over what is revealed?
a receptor lipid which acts as a signal that they cell needs to be digested
what is the key trigger of caspases?
the release of cytochrome C from the mitochondria
where is cytochrome C found?
in the inner membrane space of the mitochdonra
how is cytochrome C used in cell death?
the release of it can act as a trigger
how is cytochrome C released from mitochrondria?
pores in the membrane
what is an apoptosome?
wheel of proteins that is a platform for pro-caspase to bind
then other things can bind also activating things
what key family of proteins are there for cytochromes?
BcL-2
what are they two types of BcL proteins?
pro- surivial
pro- apoptotic
how are pro-apoptotic BCL proteins found in the cell?
found in the cell bound up to other proteins, not functional, inactive
how do pro-apoptotic BcL proteins work?
on receiving a stress signal, move to mitochondria and insert into membrane forming large pores
pores allow cytochrome C out
How do pro-survival BcL proteins work?
bind to the mitochondrai preventing apoptosis
guard the membrane
how do the proteins decide cell fate?
if lots of survival ones, lots of apoptotic ones needed to fate death
but if all survival ones are used up then pores can still be made and death occurs
need a balance
where do Bcl-2 proteins act?
on the mitochondria to regulate the formation of pores in outer membrane
what does the release of cytochrome C lead to?
formation of apoptosome and activation of the caspase cascade