Autophagy Flashcards
cytological EM
vesicles containing cytoplasm adjacent to vacuole
cytological light microscopy
autophagic-cytoplasm containing bodies on vacuole
TOR
- Ser/Thr kinase
- master regulator
- suppresses autophagy and regulates 26SP
- ATG13 phosphorylation
- no ATG1 kinase assembly
Cytology
- ATG8 and 12 UBLs are PAS
- TOR inactivation: activated ATG1 kinase phosphorylates ATG4, ATG9
- small ATG9 vesicles localise to PIS
- ATG9 lipidates ATG8
- isolation membrane forms at or near ER
- thins (direct transfer of lipids via small vesicles by ATG8-PE), expands, curves (stabilised by actin sandwich, ATG8-PE binds ATG12-5-16), becomes spherical (requires COPII-ATG2 recruitment)
- pore closes (ATG9, ESCRT-mediated fission)
- autophagosome
- lysosome/vacuole translocation
- outer membrane fusion (v and t snares)
- hydrolase degradation and recycling
IM
- phagophore
- small, flattened
autophagosome
double-membrane bound
ATG1 kinase
multiple complices assembles to form an autophagosomal assembly platform
ATG9
- phosphorylated by ATG1 kinase
- multi-spanning membrane protein
ATG4 protease
catalyses ATG8-PE delipidation
In vitro liposomes
tethering, hemifusion and fusion
microautophagy
direct invagination
chaperone-mediated
Hsc70
selective autophagy
- autophagy receptors bypass TOR
ATG8-interacting-motif (AIM)
- short, 4 residue core sequences in hydrophobic patch
- ## phosphorylation activation
Ub in selective autophagy
- labels cargo and bind to ATG8
Mitophagy
- E3 = Parkin
- PINK1
No parkinsons
- PINK goes through TOM translocon into mitochondria for degradation
- auto-inhibited Parkin
Feedforward in PARKIN
PINK1 phosphorylation creates more Parkin binding sites on MOM
Chlorophagy
- dark treatment, leaf senescence, photo damage
chloroplast recycling
rubisco containing bodies
neurodegeneration
insoluble aggregate neutralisation declines w age
amyloid-beta, alpha-synuclein and huntingtin
affect 26SP and autophagy