What do cells do when they are “hungry”?
• Eukaryotic cells cope with starving conditions
by eating their own components, a process
called
• AUTOPHAGY “self-eating”
Christian de Duve
• How insulin acted on liver cells?
• Aim: To determine the location of an enzyme called
glucose-6-phosphatase inside the cells
• The serendipity
• Nobel Prize in Physiology or Medicine in 1974
Overview
• What is Lysosome?
• Types of Lysosome
• Formation & Structure
• Lysosomal Enzymes
• FUNCTIONS
A bag of digestive enzymes
For Suicide: A Suicidal Bag
For disposing waste: A waste disposal
system
For Recycling: A recycling plant
has not yet been engaged in any cellular activity
Secondary lysosomes
• digestive vacuole, residual vacuole,
autophagic vacuole
STRUCTURE
A single biomembrane surrounds enzyme-rich matrix
Matrix varies in density:
homogeneous in primary lysosomes
in secondary lysosomes the matrix contains various inclusions (e.g.,
partially digested organelles or bacteria, etc.)
Matrix consists of many different hydrolytic enzymes
and can digest every cell component.
Acid Phosphatase = classic, marker enzyme; used to demonstrate the
presence of lysosomes in animal tissues
Oligosaccharide processing in Golgi compartments
ER
Lysosome Plasma
Membrane
EXTRACELLULAR FUNCTIONS
• Removal of cells and Extracellular material
• Tadpole tail, wolfian duct, mullers duct
• Extracellular Digestion-Bone remodeling
(rheumatoid arthritis)
• Acrosome
Protein degradation
(1) by eliminating the need for complex waste
management systems and
(2) by providing the cells with new building
blocks that don’t need to be “purchased”
externally.
Fluorescently-labelled protein
Noboru Mizushima (2004)
• Formation of autophagosome
• Pictures every five minutes
Which membrane in the cell gives rise to phagophores?
Jennifer Lippincott-Schwartz (2010)
• outer membrane of the mitochondria was the main
membrane source, with some contribution from the
endoplasmic reticulum
Lysosomal storage
diseases
Lysosomal storage diseases
• Accumulation of undigested substrates in lysosome
• pathological consequences most often in the
nervous system
• mutation in a structural gene that codes for an
individual lysosomal hydrolase
Lysosomal storage diseases
• Concept of lysosomal diseases by Hers
• Interested in glycogen storage diseases
– In Pompe disease the deficient enzyme had an acidic pH optimum and glycogen was
not stored in the cytoplasm but rather in an organelle surrounded by a membrane.
– Hers suggested that glycogen in Pompe disease is stored in lysosome
• Gaucher disease: Storage of glucosylceramide
– glucocerebrosidase deficiency
• Hurler’s disease
– enzyme required for the breakdown of certain types of glycosaminoglycan chains is
defective or missing
I-cell disease
Inclusion-cell disease (I-cell disease)
• almost all of the hydrolytic enzymes are missing from the
lysosomes of many cell types
• their undigested substrates accumulate in these lysosomes
• form large inclusions in the cells
• individuals rarely live beyond six or seven years
• Recessive
• all the hydrolases missing from lysosomes are found in the
blood
• The mis-sorting has been traced to a defective or missing
GlcNAc phosphotransferase
