Autophagy Flashcards
In most cell types what is the effect of autophagy on apoptosis?
It slows apoptosis and so is cytoprotective
What happens to autophagy if apoptotic caspase activity breaks a threshold?
Autophagy becomes inactivated
What happens to some autophagy proteins when cleaved by caspases?
They take on pro-apoptotic roles
What does autophagy do?
Delivers material from cytoplasmto lysosome
What are the 4 different types of autophagy?
- Nonspecific macroautophagy
- Chaperone-mediated autophagy
- Mitophagy
- Microautophagy
What is the function of mitophagy?
For damaged/redundant mitochondria
What happens in CMA (chaperone-mediated autophagy)?
Soluble proteins for degradation are taken from cytosol, binds to heatshock protein 70, and is transported through lysosomal membrane
What happens in microautophagy?
Lysosome invaginates and forms intralumenal vesicles which can be broken down by lysosomal hydrolases
What happens in macroautophagy?
Autophagosome forms which engulfs cytoplasmic cargoand seals itself to form new organelle which fuses to lysosome
What is the main regulatory complex of autophagy?
mTORC1
What is the effect of active mTORC1?
Inhibits autophagy
How does mTORC1 inhibit autophagy?
Inhibits ULK1 complex
When inhibition of ULK1 is lifted what happens?
It phosphorylates components of lipid kinase complex and generates PIP3 and recruits downstream effector proteins
What does the dual ubiquitin-like lipidation machinery do?
Covalently attaches LC3 to lipids on autophagosome membrane
Effector proteins recruited by ULK1 then activate what?
Dual ubiquitin like lipidation machinery
What is the role of LC3?
Helps recruit cargo into autophagosomes either by direct binding or via receptor proteins like p62
What happens to mTORC and autophagy after lysosomal fusion?
- Nutrients are released
- This activates mTORC1 which switches autophagy off
How does autophagic flux arise?
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)
How can autophagy be oncosuppressive?
- Involved in selective degradationn of some oncogenic proteins
- protects against tumour causing diseases
- Promotes normal mitochondrial metabolism, limiting ROS
How can autophagy support tumour growth and metastasis?
- Provides resistance to starvation
- Mobilise nutrients from other cells to promote tumour growth
- Protects against anoikis
- Can promote angiogenesis
