PHRD5015 Lecture 8 - Programmed cell death & autophagy
Home > Preview
The flashcards below were created by user
on FreezingBlue Flashcards.
ordered process of cell disassembly
sudden death/lysis of the cell
physiological reasons for cell death (2)
- 1) development
- 2) turnover
cellular changes during apoptosis
- cell condenses
- cytoskeleton & nuclear envelope break down
- cell breaks into apoptotic bodies & are removed by macrophages
family of proteins that mediate apoptosis
how are caspases activated?
by cleavage (removal of inhibitory pro-domain, then cleaved into large & small subunit)
caspase directly associated with the signaling machinery which activates apoptosis
how is the initiator caspase activated?
3 important caspase targets
- 1) actin
- 2) laminin
- 3) ICAD
protein that is part of the nuclear scaffold
protein that inhibits DNase
ICAD (inhibitor of the caspase-activated DNase)
do caspases degrade DNA?
extrinsic apoptotic pathway
- signal to initiate apoptosis comes from an outside source
- (ex: Fas)
initiator caspases for the extrinsic apoptotic pathway
3 death receptors
- 1) Fas
- 2) TNFR1
- 3) TRAILR1, TRAILR2, DR6
how are death receptors activated?
apoptotic receptor associated with heart disease
Fas in cardiomyocytes
intrinsic apoptotic pathway
signal for apoptosis is initiated by the cell itself
organelle that initiates the apoptotic signal
most notable pro-apoptotic factor in mitochondria
initiator caspase involved in the intrinsic apoptotic pathway
steps in the intrinsic pathway
- mitochondrial membrane releases cyt c -> cyt c induces aggregation of Apaf-1 -_ Apaf-1 recruits and activates casp9
- cyt c + Apaf-1 + casp9 = scaffold
pro-apoptotic (pore forming) protein involved in the intrinsic pathway
anti-apoptotic (inhibitory) protein involved in the intrinsic pathway
how do anti-apoptotic proteins function?
sequester the propapoptotic proteins to prevent pore formation
conserved domain present in the Bcl-2 family members that function as stress sensors and promote activation
major phagocytic cell type engaged in clearing apoptotic cells
"eat me" signal for macrophages
where is phosphatidyl serene normally found?
in the inner leaflet of the bilayer
what happens to apoptotic cells that are not phagocytosed?
undergo necrosis and release material that can activate an immune response and increase the likelihood of self-directed antibodies being produced
deficits in what process has been implicated in autoimmune disease (SLE in particular)?
macrophage phagocytosis of apoptotic bodies
phosphatase activated by Ca2+ that can activate the intrinsic pathway
important functions of Ca2+ in cell death (3)
- 1) taken up by mitochondria & inhibits ATP synthesis
- 2) promotes dissociation of actin filaments from the plasma membrane
- 3) activates other hydrolytic enzymes
protein that senses DNA damage
first response of p53
induce genes that will arrest the cell cycle
if DNA repair is unsuccessful, what does p53 do?
induces transcription of apoptosis activators in the Bcl-2 family
what defines ER stress?
accumulation of protein aggregates
what happens if after prolonged IRE1 activation?
activation of the intrinsic pathway through BAX activation and Bcl-2 inhibition
5 characteristics of necrosis
- 1) cell swelling followed by explosion
- 2) mitochondrial dysfunction
- 3) ATP degradation
- 4) release/activation of lysosomal enzymes
- 5) release of "danger signals"
what leads to the recruitment of inflammatory signals which cause further damage?
release of danger signals
process whereby the cell obtains necessary nutrients during times of nutrient deprivation
specific proteins activated to promote the creation of a special lysosome-like structure
structure of autophagosome
- outer membrane fuses with a lysosome
- contents of inner membrane then degraded
multi protein kinase which promotes the extension of membrane to create the autophagosome
how is the ULK complex regulated?
negative regulation by mTOR
transmembrane proteins which play multiple roles in the formation and fusion of autophagosomes
how are ATG proteins regulated
SIRT1 deacetylates and activates them
purpose of autophagy
recycle damaged cellular organs
What would you like to do?
Home > Flashcards > Print Preview