Lysosomes

Question 1

What are lysosomes?

Answer 1

Single membrane bound organelles

Question 2

What are lysosomes connected to?

Answer 2

Lysosomes are connected, through vesicular trafficking, to the trans Golgi and to late endosomes.

Question 3

How are lysosomal enzymes directed to lysosomes?

Answer 3

Mannose-6-phosphate pathway

Question 4

What can mutations in lysosomal enzymes cause?

Answer 4

Lysosomal storage diseases

Question 5

Structure of lysosomes - 8 points

Answer 5

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

Question 6

What do the lysosomal hydrolytic enzymes include? x6

Answer 6

Proteases
Lipases
Glycosidases
Nucleases
Phosphatases
Sulfatases

Question 7

Where are lysosomal hydrolases synthesised?

Answer 7

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.

Question 8

Methods of substrate delivery to lysosomes x3

Answer 8

Extra cellular substrates: endocytosis
Fluid-phase endocytosis of molecules and lipoproteins
(Includes receptor- mediated of endocytosis)
Phagocytosis of particles greater than 0.5qm

Question 9

How are intracellular substrates delivered?

Answer 9

Microautophagy
Macroautophagy
Selective transport of proteins across the lysosomal membrane

Question 10

What is microautophagy?

Answer 10

Invagination of the lysosomal membrane

Question 11

What is macroautophagy?

Answer 11

Cytosol or organelles wrapped in ER membrane, which then fuses with lysosomes

Question 12

What is receptor mediated endocytosis? Use example of LDL

Answer 12

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

Question 13

Phagocytosis of red blood cells - how many per second?

Answer 13

5 million RBC turnover per second

Question 14

How are old red blood cells degraded?

Answer 14

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

Question 15

What are the steps of phagocytosis?

Answer 15

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

Question 16

What is macroautophagy- full definition

Answer 16

Cells form double membrane vesicles, called autophagosomes, around a portion of cytoplasm. Autophagosomes ultimately fuse with lysosomes so contents degraded.

Question 17

How does the pH drop?

Answer 17

Proton pumps in membranes of lysosomes that pump proton from cytoplasm into lumen of ER. Requires a lot of ATP.

Question 18

Why do lysosomal enzymes require a low pH?

Answer 18

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.

Question 19

How are lysosomal hydrolases targeted to the ER?

Explain first few steps overview

Answer 19

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

Question 20

What is protein glycosylation in the ER?

Answer 20

Oligosaccharides attach to lysosomal enzymes.

Question 21

Explain protein glycosylation in terms of lysosomal enzymes

Answer 21

LH contain N-linked oligosaccharides.
Covalently modified in cis Golgi network.
Their mannose residues are phosphorylated .

Question 22

When does protein glycosylation occur in LH?

Answer 22

Once protein synthesis completed and signal peptide cleaved off