Lysosomes Flashcards
What is the morphology of lysosomes?
- spherical
- 200-400nm
- dense protein rich core
What is the cellular function of lysosomes?
degradative
macromolecules hydrolysed
role in apoptosis
repair plasma membrane damage
secretory lysosomes
What are lysosomal hydrolases?
nucleases
proteases/peptidases
glycosidases
lipases
How is lysosomal pH maintained?
pH 4.5 - 5
maintained by vATPase
pump protons into lysosomal lumen
How are broken down components transported into the cytosol?
transporters that are integrated into membrane
what are the 3 pathways for delivering material to lysosomes?
endocytosis
autophagy
phagocytosis
What is autophagy?
removal of cytoplasmic components for degradation
enhanced by cell starvation
what are the 3 types of autophagy?
Macroautophagy
Chaperone mediated autophagy
Microautophagy (membrane invagination)
What does macroautophagy do?
removes old organelles
aggregates proteins
envelopment of cytoplasmic material
fuses with lysosome
SNARE mediated event
How are lysosomes involved in apoptosis?
activation of cytosolic proteases - capsases
increase permeability
cathepsins cleave proteins at cytosolic pH
secondary role (not essential)
How to lysosomes aid plasma membrane repair?
damage to plasma membrane
exocytosis of lysosomes to the damaged site
triggered by Ca2+ influx - detected by lysosomal protein synaptotagmin 7
How are lysosomes involved in I-cell disease?
mutation in GNPTA encoding N-acetylglucosamine-1-phosphotransferase
form intracellular inclusions
secrete lysosomal hydrolases - not modified by enzymeand not recognised by M6P
What is Pompe disease?
auto rec mutation that encodes alpha-D-glucosidase
this cleaves glycogen into glucose - can be transported to cytosol
deficiency = abnormal accumulation of glycogen
What are symptoms of Pompe disease?
- cardiac and skeletal myopathy
- cardiorespiratory failure
How can Pompe disease be treated?
ERT
infusions of mannose-6-phosphate modified alpha-D-glucosidase
enzyme taken up by M6P & delivered to lysosomes
What is Fabry Disease?
X-linked alpha-galactosidase mutations facial abnormalities progressive organ damage deposition of glycolipid Gb3
What are the molecular mechanisms behind Fabry disease?
alpha galactosidase removes terminal galactose from Gb3
What is the treatment for Fabry disease?
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
What is ISASD?
autosomal recessive mutations - Sialin gene
facial abnormalities, mental retardation, enlarged organs
What is Salla disease?
mutations in sialin
less severe than ISASD
physical & mental impiarment
What is the molecular basis of ISASD and Salla disease?
Sialin - lysosomal membrane transporter
loss of transport = accumulation of sialic acid in lysosomes
degraded by ERAD / lose transport activity
