Lysosomal System Flashcards
What are lysosomes ?
Lysosomes are membrane bound organelles containing acid hydrolase enzymes
Function - break up waste materials and cellular debris
Formed from the Golgi apparatus
Regulation of cell growth signalling via mTOR
Describe unique nature of the lysosomal environment
Lysosomes have an ambient pH of 4.5-5.0
Contain >40 types of acid hydrolases
Lysosomal hydrolases are produced as inactive precursors
They are then only activated by proteolytic cleavage within the low pH environment of the lysosome
Lysosomal hydrolases are relatively safe outside the lysosome as they require an acid pH to work efficiently
Describe unique properties of the lysosomal membrane
Lysosomal membrane houses a V-type ATPase (proton pump) that uses energy provided by ATP hydrolysis to pump hydrogen ions into the lysosome
Membrane proteins that face the lysosomal lumen are richly glycosylated to protect them from destructive enzymes
Describe the maturation of lysosomes:
Primary lysosomes:
- haven’t entered into a digestive event
- fuse with a phagosome or late endosome and empty their hydrolytic enzymes into the lumen
- originate from the Golgi
Secondary lysosomes;
- enzymatic digestion occurs producing secondary lysosome
- after digestion, contents diffuse to cytoplasm
- undigested material remains within the lysosome as a Residual Body
Late endosomes fuse with existing lysosomes to form endolysosomes
What pathways lead to degradation in lysosomes ?
Endocytosis - endocytosed molecules are delivered in vesicles to early endosomes
Autophagy - organelle is enclosed by a double membrane to create an autophagosome which fuses with lysosome
Phagocytosis - phagocytes (macrophages, neutrophils) engulf objects to form a phagosome which is then fuses with a lysosome
Discuss the role of autophagy in health and disease:
Degradation pathway linking to lysosomes to dispose of obsolete cell organelles.
Autophagosome, a double-membrane enclosing cytosol, exists for 10-20 min before fusing with lysosome.
Provides energy and amino acids for protein synthesis, essential during stress.
Functions to eliminate viruses, bacteria, toxic protein aggregates, and obsolete organelles.
Important during embryogenesis, cell differentiation, infection, and aging-related diseases.
How Are Hydrolytic Enzymes and Membrane Proteins Delivered to Lysosomes?
In the trans-Golgi network, a M6P receptor protein binds to the M6P marker protein and sequesters it to specific areas of the trans–Golgi cisterna membrane
Lytic enzymes that are to be packaged into specific vesicles for transportation carry the mannose 6 – phosphate (M6P) marker
What are peroxisomes ?
Organelles that contain oxidative enzymes, such as D-amino acid oxidase, ureate oxidase, and catalase.
Function;
- lipid and energy metabolism
- breakdown of hydrogen peroxide to water
- reduction of reactive oxygen species
- synthesis of ether phospholipids
Describe lysosomal function:
Degradation of macromolecules
Lysosomal exocytosis
Cholesterol homeostasis
Lysosomal Mediated Apoptosis
Compare the mechanism of protein targeting for lysosomal hydrolyses (Mannose-6-P receptor mediated) to that of secretory vesicles.
Targeting signal;
- MP6 tag for LH
- no tag for SV
Describe clathrin-coated vesicles in generation of primary lysosomes:
Initiation in the Trans-Golgi Network - newly synthesized lysosomal enzymes are tagged with mannose-6-phosphate
Formation of Clathrin-Coated Vesicles - AP-1 complex, bind to both clathrin and the cytoplasmic tails of the M6P receptors
Dynamin - helps pinch vesicle off TGN
Transport to Late Endosomes
Release of Enzymes and Formation of Primary Lysosomes
Describe Labelling the Lysosomal Hydrolases in the Cis-Golgi Network & Dysfunction in I-Cell Disease:
Genetic defects in the N-Acetyl-Glucosamine (GlcNAc) phosphotransferase enzyme results in a very severe lysosomal storage condition called I-Cell Disease
In I-Cell Disease, failure to correctly tag the lysosomal hydrolases causes all the lysosomal enzymes to avoid the lysosome and be mis-directed to the cell surface
Individuals with I-Cell Disease show high levels of acid hydrolases in their blood
