Lecture 16 - lysosymes Flashcards
Lysosomes
Activity maximal at pH 5 - maintained by proton pump (vacuolar ATPase), helps denature proteins, allowing for better access for proteases
~40 hydrolytic enzymes - degrade proteins, nucleic acids, sugars, lipids, and pump products to the cytoplasm
What stops lysosomal membrane proteins from being broken down?
High amounts of glycosylation
How are lysosomal enzymes made?
Made at ER, transported to Golgi, sorted into clathrin-coated vesicles at the TGN, moved into late endosomes, late endosomes fuse with lysosomes
Tagged with M6P (Mannose-6-phosphate)
How is M6P added to lysosomal enzymes?
1 - addition of phosphoGlcNAc to mannose
2 - removal of GlcNAc to leave M6P
Lysosomal storage diseases
Often genetic disorders
Result in accumulation of undigested substances due to a loss of hydrolytic enzymes from lysosomes
Is M6P the only way lysosomal enzymes are tagged to the lysosome?
No, in diseases where M6P tagging is malfunctioned and results in insufficient hydrolytic enzymes within the lysosome, hepatocytes have been found to be working perfectly normal, suggesting an alternative M6P-independent pathway
Pathways to lysosomal degradation
Phagocytosis
Endocytosis
Macropinocytosis
Autophagy
Autophagy
Self-eating
- Removal of protein aggregates
- Intracellular bacteria
- Regions of cytoplasm during starvation
Defects result in neurodegeneration/cancer cells
Secretory lysosomes
Specialised lysosomes found in some cell types - melanocytes, cytotyxic T-cells, sperm cells
Autophagy process
1 - Induction by signals (typically ubiquitin)
2 - ATG proteins act sequentially to generate enclosed double membrane autophagosome
3 - Autophagosome fuses with lysosome
Cytotoxic t-cell
Binds to target cell
- Fuses with PM
- Releases lytic granules - perforin, granzyme B
- Cell death occurs
Perforin
Forms pores in target cells
Granzyme B
Enters cells and induces apoptosis
Vacuoles
Found in plant and fungi
Occupy >30% of cell volume
Highly versatile lysosomes:
* Storage
* Hydrolytic enzymes
* Regulate turgor and cell size
How do vacuoles affect turgor and cell size
Varying osmotic pressure of vacuole and cytoplasm - varying synthesis/polymer breakdown rates and metabolites moving across the vacuole/PM
