autophagy 1 Flashcards
what is autophagy
self eating
intracellular material is degraded within the lysosome/ vacuole and macromolecular constituents are recycled
stress response pathway
sources of membrane for autophagosome formation
er, pm, mitochondria and golgi A
er derived autophagosomes
er assiciates with early ap structures
atg48 mutant - unclosed aps attached to er
er is present on inside and outside of forming ap
mitochondrial origin of ap
form the outer mitochondrial membrane
requires direct mitochon to er contact
facilitates transfer of phosphatidyl serine that is converted to phosphatidyl ethanolamine (PE)
pe is an essnetial ap lipid component
3 kinase complexes that regulate ap formation
mtorc1, ulk1, pi3k
mtorc1
inhibits ulk1 in presence of aa’s and gf’s
after aa and gf removal, mtorc1 dissociates from ulk1
ulk1 becomes active and phosphorylates atg13, atg101 and fip200
high levels of glucose inhibits ampk
increase in amp/atp ratio activates ampk
ampk phosphorylates mtorc1 and phosphorylates ulk1
building an autophagosome
ub like conjugation drives ap expansion
ub like modifiers are at the heart of ap formation
pi3p helps ap grow
ub like modifiers
atg8/lc3/gabarap and atg 12 and atg5 have ub like folds
e1/e2/e3 ub conjugation drives ap expansion
atg12-atg5-atg16 complex acts as e3 to conjugate atg8/lc3 onto autophagosomal membrane
atg8/lc3 proteins are attached to lipids not lysine residues unlike Ub
how is the correct cargo seleceted to be degraded
interactions between autophagy receptors and ub like proteins form molecular basis for selective autophagy