Cell Quality Control Flashcards
How do cells mitigate the aggregation of unfolded proteins?
Chaperones- These molecules bind to unfolded proteins and keep them from binding to other unfolded proteins
Degradation mechanisms for unfolded proteins
Why do unfolded proteins cause pathology?
aggregate via hydrophobic interactions and cause problems in brain and other organs
How do cells know a protein is unfolded?
glycosylation pattern, acts as a timer
Where are unfolded proteins most damaging in the cell and why?
ER, less volume so get higher concentration faster
How does cell act to promote folding via glycosylation patterns?
In cell, glucosidase cleaves glucose from sugar side chain when protein in folded, if the protein in not properly folded, glucosyltransferase adds add glucose residue back so protein can bind to calnexin
Unfolded proteins binds to calnexin (chaperone that recognizes a certain glysolylation pattern) in cell membrane and keeps unfolded protein from leaving the ER, giving it a chance to fold
If the protein has been unfolded in the cell for too long, it can encounter mannosidase that removes manose from the sugar chain and targets the protein for degradation
How is unfolded protein moved out of the ER?
EDEM membrane protein binds to sugar chain cleaved by mannosidase and transports unfolded protein into cystol where it is ubiquitylated and degraded
How does cell respond to unfolded proteins?
1) increase lipid synthesis
2) increase chaperones
3) decrease translation of protiens
What are the three sensors that detect concentrations of unfolded proteins in the ER and how do they respond?
1) IRE 1: usually inactive and bound to chaperones but with increase in unfolded proteins, chaperones go to unfolded proteins and IRE1 is activated, transcribes a TF that increases chaperones and lipid synth.
2) PERK: increases translation (prolonged activation triggers apoptosis)
3) ATF: chaperones removes like IRE1, AFT moves to golgi, catalytic domain cleaved, becomes TF, TF activates gene for chaperones and lipid synth (same mechanism for sterol response factor in cholesterol)
What is the role of autophagy in the cell?
important for degrading proteins and organelles that are nonfunctioning
Immune response
What are the proteins that mediate autophagy?
Atg proteins , both specific and non specific
What is the difference bt apoptosis and necrosis?
Apoptosis is ordered cell death, doesn’t release material from cell into environment, binds with lysosomes and is degraded
What is a pathway for apoptosis?
PERK and ATF catalyze channels in outer membrane of mitochondria that let in cytochrome c which activates caspases which activate proteases that degrade the cell
