Lysosomes

Question 1

lysosomes play a role in:

Answer 1

Homeostasis
cell death
metamorphosis
fertilization

Question 2

how do lysosomes form? what is their general structure?

Answer 2

by the maturation of Late Endosomes.
V-type proton pumps acidify the lumen
~40 hydrolytic enzymes (acid hydrolases) fill the lysosome
transmembrane transporters in the lysosomal bilayer transport hydrolysis products out to cytosol

Question 3

what happens if an acid hydrolase gets into the cytosol? what is required for optimal acid hydrolase activity

Answer 3

its activity would be greatly reduced because the pH of the cytosol is too high. acid hydrolases function best at low pH like inside the lysosome and they also require activation by proteolytic cleavage

Question 4

how are lysosomal acid hydrolases directed to the lysosomes?

Answer 4

by mannose-6-phosphate (M6P) attached to the outer branches of their N-linked glycosylation. M6P creates a sorting signal and directs acid hydrolases to lysosomes

Question 5

what is the process of delivering acid hydrolases to the lysosomes?

Answer 5

1. the M6P label is recognized by a transmembrane cargo receptor protein within the bilayer of trans Golgi
2. acid hydrolases are recruited into transport vesicles that bud from trans golgi and go to early endosomes
3. acid hydrolases unbind from cargo receptors at early Endosomes because pH is more acidic and M6P binding is pH dependent

Question 6

what organelle in plants is similar to lysosomes in animals?

Answer 6

vacuoles. vacuoles can occupy a huge percentage of pant cell volume and have many functions including producing turgor pressure with their large size

Question 7

what is the pathway of endocytosed material?

Answer 7

first transported to early Endosome, then multi-vesicular body, then a late Endosome, and finally to a lysosome for digestion

Question 8

what is the function of intralumenal vesicles in digestion?

Answer 8

they allow for digestion of phospholipid bilayers and transmembrane proteins, things on the extracellular surface. many would be found in a late Endosome

Question 9

lysosomes receive materials through three processes

Answer 9

1. micropinocytosis
2. phagocytosis
3. autophagy: self eating. degrades unwanted proteins and organelles. recycles materials that proteosomes cannot (macromolecules, protein aggregates, entire organelles)
   - can be non-selective or selective

Question 10

parkinson disease

Answer 10

caused by mutations in PINK1 or Parkin.
Pink1 is a protein kinase that accumulates on the surface of damaged mitochondria and Parkin is a ubiquitin ligase that is recruited by Pink1. together they mark a damaged mitochondria for engulfment within an autophagosome. mutations in Pink1 and Parkin may lead to death of neurons required for body movements

Question 11

What are autophagosomes and how do they function?

Answer 11

double bilayers that engulf organelles or cytoplasm.
fusion of an autophagosome with a lysosome or late Endosome is mediated by SNARE proteins. the fusion leads to digestion of the autophagosome and its contents

Question 12

lysosomal storage disorders

Answer 12

most commonly caused by mutation in a gene encoding a single lysosomal hydrolase. hydrolase is not expressed or does not function properly so accumulation of undigested macromolecules occurs.
Tay-Sachs disease, Hurler syndrome, Inclusion cell disease

Question 13

how does inclusion cell disease occur?

Answer 13

the enzyme that attaches the M6P label to acid hydrolases is mutated so lysosomal hydrolases are not sent to lysosomes but are instead secreted into extracellular fluid.undigested substrates accumulate in lysosomes and form large inclusions