Autophagy Flashcards

1
Q

In most cell types what is the effect of autophagy on apoptosis?

A

It slows apoptosis and so is cytoprotective

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2
Q

What happens to autophagy if apoptotic caspase activity breaks a threshold?

A

Autophagy becomes inactivated

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3
Q

What happens to some autophagy proteins when cleaved by caspases?

A

They take on pro-apoptotic roles

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4
Q

What does autophagy do?

A

Delivers material from cytoplasmto lysosome

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5
Q

What are the 4 different types of autophagy?

A
  • Nonspecific macroautophagy
  • Chaperone-mediated autophagy
  • Mitophagy
  • Microautophagy
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6
Q

What is the function of mitophagy?

A

For damaged/redundant mitochondria

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7
Q

What happens in CMA (chaperone-mediated autophagy)?

A

Soluble proteins for degradation are taken from cytosol, binds to heatshock protein 70, and is transported through lysosomal membrane

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8
Q

What happens in microautophagy?

A

Lysosome invaginates and forms intralumenal vesicles which can be broken down by lysosomal hydrolases

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9
Q

What happens in macroautophagy?

A

Autophagosome forms which engulfs cytoplasmic cargoand seals itself to form new organelle which fuses to lysosome

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10
Q

What is the main regulatory complex of autophagy?

A

mTORC1

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11
Q

What is the effect of active mTORC1?

A

Inhibits autophagy

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12
Q

How does mTORC1 inhibit autophagy?

A

Inhibits ULK1 complex

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13
Q

When inhibition of ULK1 is lifted what happens?

A

It phosphorylates components of lipid kinase complex and generates PIP3 and recruits downstream effector proteins

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14
Q

What does the dual ubiquitin-like lipidation machinery do?

A

Covalently attaches LC3 to lipids on autophagosome membrane

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15
Q

Effector proteins recruited by ULK1 then activate what?

A

Dual ubiquitin like lipidation machinery

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16
Q

What is the role of LC3?

A

Helps recruit cargo into autophagosomes either by direct binding or via receptor proteins like p62

17
Q

What happens to mTORC and autophagy after lysosomal fusion?

A
  • Nutrients are released
  • This activates mTORC1 which switches autophagy off
18
Q

How does autophagic flux arise?

A

Fusion of lysosomes to form autolysosomes

(if lysosomal function is inhibited get a build up of autophagosomes so might think autophagy is active but autophagosomes just have nowhere to go)

19
Q

How can autophagy be oncosuppressive?

A
  • Involved in selective degradationn of some oncogenic proteins
  • protects against tumour causing diseases
  • Promotes normal mitochondrial metabolism, limiting ROS
20
Q

How can autophagy support tumour growth and metastasis?

A
  • Provides resistance to starvation
  • Mobilise nutrients from other cells to promote tumour growth
  • Protects against anoikis
  • Can promote angiogenesis