13-Autophagy in mammals

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Describe autophagy
'self eating' - conserved in eukaryotes, process in which cytoplasmic material is delivered to the lysosome inside a double-membraned vesicles for degradation.
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Why do cells use autophagy?
If molecules for energy not available – autophagy can help with this, Providing amino acids, lipids, nucleotides&sugars under low nutrient conditions, Cell differentiation&developmental remodelling, Removal of aggregates, damaged organelles&pathogens
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Lysosome is central organelle for intracellular degradation ->? in early endosomes?
->hydrolytic enzymes delivered via the secretory pathway->acitvates hydrolytic activity in the lysosome.Significance: recycling of cell material
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Lysosome is central organelle for intracellular degradation ->? in late endosomes?
-> Delivery of extracellular and PM proteins by endocytic pathway (are involved in the transport and activation of the hydrolases late on in the lysosomes)
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How do lysosomes contribute to autophagy?
Lysosome also essential for degradation of intracellular components  Autophagy
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What are the different types of autophagy?
chaperone mediated autophagy/microautophagy/xenophagy/mitophagy, pexophagy, reticulophagy.../macroautophagy
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Define autophagosome
a unique organelle that mediates autophagy, Double-membraned vesicle
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How do autophagosomes form?
Autophagy-related proteins (Atg) form autophagosome: PAS – Preautophagosomal structure>Atg1/Unc-51-like kinase (ULK1/2) complex>Class III PI3K complex (e.g. ATG6/Beclin1, Atg14) >Atg18/Atg21/WD-repeat proteins>Atg12>Atg8/LC3conjugation systems>Atg9TM
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Atophagosome formatin is also dependent on what?
Autophagosome formation is also dependent on vesicles and structures from PM which fuse with early endosome which converts into late endosomes which fuse with lysosomes giving it specificity to fuse with autophagosome OR late endosomes can fuse w a-p
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Is autophagy selective or non-selective?
Autophagy is quite selective-proteins involved in loading of autophagosomes during formation of isolation membrane give specificity to cargo loading that goes to autophagosome&determine what needs to be degraded
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How is degredation by autophagy induced?
bacteria caught by isolation membrane to form autophagosome TLR (immunity receptors) can also initiate autophagy when they recognise bacteria LIR always found in sequestosome and so is UB_ (ubiquitin binding domains)
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What happens when something is polyubiquitylated in a cell?
As soon as something is polyubiquitylated it is usually degraded in a cell
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Different pathways of autophagy degredation?
small proteins = proteasome degrades ubiquitylated proteins/ bigger structures are too big to be degraded by the proteasome and so are labelled to be autophagosome substrates  autophagosome formed around aggregates of ubiquitylated proteins->degrade
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Possible effects of autophagy dysfunction?
Neurodegeneration, cancerm infectionns and immunity, liver disease, ageing, myopathies
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Why is it difficult to study autophagy?
Difficulty: Multiple functions of genes ->Pleiotropic effects of genes(unrelated to autophagy)->if you knock out gene you think has autophagy effects and something happens unrelated to autophagy
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How can we study autophagy to find which enes and metabolites are involves?
screen chemical libraries = randomly test chemical molecules and randomly test them for function (activating or inhibiting) in autophagy andmake list
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Genetic and chemetic approach to studying autophagy?
Take drug/chemical and combine it with genetics  treat cells lacking a certain autophagy gene-> give drug to override genetic deficiencies
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Card 2

Front

Why do cells use autophagy?

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If molecules for energy not available – autophagy can help with this, Providing amino acids, lipids, nucleotides&sugars under low nutrient conditions, Cell differentiation&developmental remodelling, Removal of aggregates, damaged organelles&pathogens

Card 3

Front

Lysosome is central organelle for intracellular degradation ->? in early endosomes?

Back

Preview of the front of card 3

Card 4

Front

Lysosome is central organelle for intracellular degradation ->? in late endosomes?

Back

Preview of the front of card 4

Card 5

Front

How do lysosomes contribute to autophagy?

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