Lecture 7 : Cell biology of Disease

Question 1

what is the mutation that causes build up of lactic acid in blood via pyruvate accumulation (CONGENITAL LACTIC ACIDOSIS)

Answer 1

arginine to proline
proline breaks the helix in mitochondrial targeting sequence

Question 2

mutation that causes less insulin to be made

Answer 2

arginine to cysteine
means insuling signal sequence catn interact properly with Sec61 and not translocated into ER

Question 3

what can happen if insulin incorrectly localsied to cytosol

Answer 3

toxic agrregates
beta-cell death

Question 4

2 potential consequences of proteins that incorrectly localise to cytosol

Answer 4

aggregate - autophagy, lysosomes eat it nom nom
or
misfold then get degraded by proteasome back into AAs

Question 5

what marks misfolded or short lived proteins to get degraded via proteolysis

Answer 5

ubiquitin

Question 6

example of a potentially dangerous msifolded protein

Answer 6

ion channel that’s always open

Question 7

what binds to misfolded protein to stop them from leaving the ER

Answer 7

chaperone proteins
will have sequences that make sure they stay in ER (e.g. KDEL)

Question 8

what type of channel is CFTR and what does it allow

Answer 8

chloride channel
in epithelial cells, water moves out
makes sure mucus is hydrated so cilia can their job

Question 9

what does dF508 mutation effect in CFTR

Answer 9

cant fold properly
gets retained by ER control system
so doesnt reach plasma membrane

Question 10

what is ERAD

Answer 10

ER associated degradation
the mechanism that means misfolded proteins stay in ER then get degraded by proteasome

Question 11

what effect to drugs like Lumacaftor have on dF508 CFTR

Answer 11

corrects the misfolding so it doesnt get stuck in ER
(some other drugs also increase channel opening e.g. Kaftrio/Orkambi)

Question 12

what type of diseases do degrading misofolded proteins usually cause

Answer 12

loss of function

Question 13

what type of diseases do acculumated misfolded proteins usually cause

Answer 13

gain of function

Question 14

cell’s response to build up of misfoldedproteins (if they’re not getting protealysed)

Answer 14

binds to stress sensors
triggeres unfolded protein response (UPR)

Question 15

Effects of UPR

Answer 15

increases chaperones
inhibits protein synthesis
tries to restore hometostasis
IF CANT be restored
then can trigger apoptosis :(