Lysosomes Flashcards
What are lysosomes?
Single membrane bound organelles
What are lysosomes connected to?
Lysosomes are connected, through vesicular trafficking, to the trans Golgi and to late endosomes.
How are lysosomal enzymes directed to lysosomes?
Mannose-6-phosphate pathway
What can mutations in lysosomal enzymes cause?
Lysosomal storage diseases
Structure of lysosomes - 8 points
Relatively dense Single membrane bound Entire vesicles can be inside them Can appear dark due to materials that need degrading ~100 lysosomes per cell ~40 hydrolytic enzymes Heterogeneous contents pH 4-5
What do the lysosomal hydrolytic enzymes include? x6
Proteases Lipases Glycosidases Nucleases Phosphatases Sulfatases
Where are lysosomal hydrolases synthesised?
In the ER. Transported via vesicles to the cis side of the Golgi and modified.
Vesicles reform at the trans side of the Golgi and then transported into lysosomes.
Methods of substrate delivery to lysosomes x3
Extra cellular substrates: endocytosis
Fluid-phase endocytosis of molecules and lipoproteins
(Includes receptor- mediated of endocytosis)
Phagocytosis of particles greater than 0.5qm
How are intracellular substrates delivered?
Microautophagy
Macroautophagy
Selective transport of proteins across the lysosomal membrane
What is microautophagy?
Invagination of the lysosomal membrane
What is macroautophagy?
Cytosol or organelles wrapped in ER membrane, which then fuses with lysosomes
What is receptor mediated endocytosis? Use example of LDL
LDL, a cholesteryl Ester (steroid molecules and fatty acid)
Coated pits can invaginate and pinch off
pH drops leading to dissociation so LDL particles end up in endo/lysosomes where LDL is hydrolysed by lipase
Cholesterol and fatty acid
Phagocytosis of red blood cells - how many per second?
5 million RBC turnover per second
How are old red blood cells degraded?
They are taken up by macrophages.
Macrophage attaches to RBC and starts to engulf it. Can engulf 2 at a time.
Plasma membrane of macrophage wraps around RBC
What are the steps of phagocytosis?
1) Engulfment- plasma membrane wraps around particle - becomes a phagosome
2) Lysosome fusion- lysosome fuses with phagosome. pH drops (optimum for lysosomal enzymes)
3) digestion of contents
4) sugars/lipids/ any breakdown products can be recycled e.g. for metabolised
What is macroautophagy- full definition
Cells form double membrane vesicles, called autophagosomes, around a portion of cytoplasm. Autophagosomes ultimately fuse with lysosomes so contents degraded.
How does the pH drop?
Proton pumps in membranes of lysosomes that pump proton from cytoplasm into lumen of ER. Requires a lot of ATP.
Why do lysosomal enzymes require a low pH?
Not active at neutral pH.
If lysosomal enzymes were to escape into the cytoplasm they would not be active at that neutral pH and not cause damage.
How are lysosomal hydrolases targeted to the ER?
Explain first few steps overview
Lysosomal hydrolases originally made in ER
Synthesis starts at ribosomes.
Signal peptide emerges.
Complex with SRP attaches to channel in ER membrane
Synthesised protein transported to ER
What is protein glycosylation in the ER?
Oligosaccharides attach to lysosomal enzymes.
Explain protein glycosylation in terms of lysosomal enzymes
LH contain N-linked oligosaccharides.
Covalently modified in cis Golgi network.
Their mannose residues are phosphorylated .
When does protein glycosylation occur in LH?
Once protein synthesis completed and signal peptide cleaved off
