Autophagy Flashcards
1
Q
Function of lysosomes?
A
- Organelle that degrades either
- Obsolete cell components
- Material taken into cell by endocytosis or phagocytosis.
2
Q
How do lysosomes function?
A
- Contain enzymes that digest nucleic acids, proteins, carbs, and lipids
- All work at acidic pH.
3
Q
How are things shipped to the lysosome?
A
- Tagged with a signal protein (Mannose 6-phosphate) M6P
4
Q
How to make Mannose 6-phosphate?
A
- Addition and initail processing of N-linked oligosaccharide precursors occur in rough ER
- M6P signal generated in cis-Golgi
- N-acetylglucosamine phosphotransferase transfers phosphorylated N-acetylglucosamine (GlcNAc) group to carbon atom 6 of one of mannose residues.
- Lysosomal protein released from phosphotransferase
- GlcNAc group removed by phosphodiesterase, leaving phosphorylated mannose residue.
5
Q
Steps in traffiking of soluble lysosomal proteins from the trans-golgi and cell surface to lysosomes
A
- Lysosomal proteins enter clathrin-coated vesicles
- Clathrin coat is removed
- Uncoated vesicles fuse with late endosomes
- Late endosome containing dephosphorylated lysosomal proteins fuses with lysosome.
- Some M6P receptors delivered to cell surface
- Some phosphorylated lysosomal proteins secreted and retrieved by endocytosis in clathrin-coated pits
- Clathrin coat removed from vesicle
- Endocytic vesicles fuses with late endosomes.
6
Q
Lysosomal Storage diseases
A
- Caused by absense of one or more lysosomal enzymes
- Undigested glycolipids and extracellular components accumulate in lysosomes as large inclusions
7
Q
Definition of autophagy
A
- Regulated process by which cytosolic components and organelles are delivered to lysosomes, degraded and recycled
- Serves normal housekeeping function
- Usually doesn’t kill cell but cell can die if process deregulated
8
Q
What induces autophagy?
A
- Environmental cues
- Starvation
- High temp
- Low O2
- Hormonal stimulation
- Intracellular stress
- Damaged organelles
- Accumulation of misfolded or aggregated proteins
- Microbial and viral infection.
9
Q
3 Types of Autophagy?
A
Micro-, Macro-, Chaperone-mediated
10
Q
What is microautophagy?
A
- Cytosolic components taken up directly by lysosome
- Lysosomal membrane invaginates
11
Q
What is macrautophagy?
A
- Cytosolic components delivered to lysosome by vesicle called autophagosome
- Fuses with lysosome to form autolysosome
12
Q
Macroautophagy pathway?
A
- Three steps to form autophagosome
- Nucleation
- Growth and completion/elongation
- Targeting and fusion/docking
13
Q
What is the role of Atg5 in Autosophagosome formation?
A
Binds with Atg12 to form dimer, then the dimer associates with Atg16 to form the vesicle that was started by Atg8
14
Q
What is the role of Atg8 in Autosophagosome formation?
A
- It is required for initial vesicle fusion
- Covalently linked to phosphatidylethanolamine
15
Q
Regulation of Macroautophagy?
A
- Macroautophagy regulated at autophagosome formation
- During periods of high/sufficient nutrient levels, autophagy not activated.
- mTOR phosphorylates regulatory protein upstream of Atg8, 12, 15.
- This prevents induction of autophagy
- mTOR phosphorylates regulatory protein upstream of Atg8, 12, 15.
- During starvation or stress
- mTOR dissociates from complex
- Autophagic induction proteins activated by phosphatases.
- During periods of high/sufficient nutrient levels, autophagy not activated.
