Lysosomes

Question 1

What is the morphology of lysosomes?

Answer 1

• spherical
• 200-400nm
• dense protein rich core

Question 2

What is the cellular function of lysosomes?

Answer 2

degradative
macromolecules hydrolysed

role in apoptosis
repair plasma membrane damage
secretory lysosomes

Question 3

What are lysosomal hydrolases?

Answer 3

nucleases
proteases/peptidases
glycosidases
lipases

Question 4

How is lysosomal pH maintained?

Answer 4

pH 4.5 - 5
maintained by vATPase
pump protons into lysosomal lumen

Question 5

How are broken down components transported into the cytosol?

Answer 5

transporters that are integrated into membrane

Question 6

what are the 3 pathways for delivering material to lysosomes?

Answer 6

endocytosis
autophagy
phagocytosis

Question 7

What is autophagy?

Answer 7

removal of cytoplasmic components for degradation

enhanced by cell starvation

Question 8

what are the 3 types of autophagy?

Answer 8

Macroautophagy
Chaperone mediated autophagy
Microautophagy (membrane invagination)

Question 9

What does macroautophagy do?

Answer 9

removes old organelles
aggregates proteins
envelopment of cytoplasmic material
fuses with lysosome

SNARE mediated event

Question 10

How are lysosomes involved in apoptosis?

Answer 10

activation of cytosolic proteases - capsases

increase permeability

cathepsins cleave proteins at cytosolic pH

secondary role (not essential)

Question 11

How to lysosomes aid plasma membrane repair?

Answer 11

damage to plasma membrane

exocytosis of lysosomes to the damaged site

triggered by Ca2+ influx - detected by lysosomal protein synaptotagmin 7

Question 12

How are lysosomes involved in I-cell disease?

Answer 12

mutation in GNPTA encoding N-acetylglucosamine-1-phosphotransferase

form intracellular inclusions

secrete lysosomal hydrolases - not modified by enzymeand not recognised by M6P

Question 13

What is Pompe disease?

Answer 13

auto rec mutation that encodes alpha-D-glucosidase

this cleaves glycogen into glucose - can be transported to cytosol

deficiency = abnormal accumulation of glycogen

Question 14

What are symptoms of Pompe disease?

Answer 14

• cardiac and skeletal myopathy

- cardiorespiratory failure

Question 15

How can Pompe disease be treated?

Answer 15

ERT
infusions of mannose-6-phosphate modified alpha-D-glucosidase

enzyme taken up by M6P & delivered to lysosomes

Question 16

What is Fabry Disease?

Answer 16

X-linked
alpha-galactosidase mutations 
facial abnormalities
progressive organ damage
deposition of glycolipid Gb3

Question 17

What are the molecular mechanisms behind Fabry disease?

Answer 17

alpha galactosidase removes terminal galactose from Gb3

Question 18

What is the treatment for Fabry disease?

Answer 18

ERT
mannose-6-phosphate modified form of the enzyme

Migalastat
binds to mutants in ER and stabilises them so they can be trafficked to lysosomes

Question 19

What is ISASD?

Answer 19

autosomal recessive mutations - Sialin gene

facial abnormalities, mental retardation, enlarged organs

Question 20

What is Salla disease?

Answer 20

mutations in sialin
less severe than ISASD
physical & mental impiarment

Question 21

What is the molecular basis of ISASD and Salla disease?

Answer 21

Sialin - lysosomal membrane transporter
loss of transport = accumulation of sialic acid in lysosomes

degraded by ERAD / lose transport activity