Professional Documents
Culture Documents
Lysosomes Presentation
Lysosomes Presentation
Lysosomes are discovered by a Belgian cytologist, Christian Ren de Duve (also peroxisomes) in 1949 and won a Nobel prize. Alex Novikoff from the University of Vermont took the first electron micrographs of the new organelle. In Greek lysis means destruction or dissolution and soma means body.
It is roughly spherical or elongated, single membrane bound cell organelle and the size ranges from 0.1 to 1.2m. They are acidic, with a pH of 4.6 favouring the enzyme activity, which is maintained by pumping protons from the cytosol that has a pH of 7.2 through proton pumps. They enclose various soluble hydrolytic enzymes. These are also called as suicidal bags of the cell and also little stomach of the cell. The absence of a single enzyme leads to several disorders in humans. These are present exclusively in animal cells (in plant and fungal cells vacuoles perform similar function).
4
Glycoprotein rich membrane. Lysosomal associated membrane proteins(lamp) and Lysosomal integral membrane proteins(limp) Unusual lipids lyso-bisphosphatidic acid, thought to protect lysosomal membrane lipids from action of lumenal lipases
5
pH 5-5.5 pH 6-6.5
MANNOSE-6-PHOSPHATE RECEPTOR
10
About 50 acid hydrolases have been found. Acid nucleases such as ribonuclease II, deoxyribonuclease II and exonuclease hydrolyze nucleic acids to nucleosides. Acid proteases such as cathepsin-L, cathepsin-D and carboxypeptidase-A hydrolyze proteins to amino acids and dipeptides.
11
Acid glycosidases such as -galactosidase, glucosidase and -mannosidase hydrolyze polysaccharides to monosaccharides and disaccharides Acid lipases such as phospholipase-A1 and triacylglycerol lipase hydrolyze lipids to fatty acids Acid phosphatase hydrolyzes phosphate esters to inorganic phosphates Arylsulfatase B hydrolyzes sulfur esters to inorganic sulfates
12
13
2.
3. 4. 5. 6.
Autophagy Role in endocytosis and phagocytosis Role in apoptosis Role in fertilization Role in repairing cell membrane Exocytosis(secretion)
14
1. WHAT IS AUTOPHAGY?
15
Autophagy is the intra cellular process, by which cell degrades its own components using lysosomal machinery and recycles the molecules. Damaged macromolecules, malformed proteins, non-functional, damaged and old organelles are all broken down by the lysosomal enzymes and thus, helps in the organelle turnover, that is, the regulated destruction of the cells own organelles and their replacement. During starvation or nutrient-limiting conditions, autophagy of normal organelles occurs, thus helping to maintain the level of nutrients required for the normal cellular processes.
16
2. WHAT IS ENDOCYTOSIS?
Endocytosis is the process for the cellular uptake of foreign material. "Endocytosis came from the word endo which means within, cyt meaning cell and -osis meaning process. Types of endocytosis A. Phagocytosis B. Receptor-mediated endocytosis C. Potocytosis D. Macropinocytosis
17
18
A. WHAT IS PHAGOCYTOSIS?
19
Brings about the uptake of specific extracellular macromolecules (ligands) following their binding to receptors on the external surface of the plasma membrane. Is an important process in exogenous antigen processing(endocytic pathway).
20
21
WHAT IS CLATHRIN?
Clathrin-coated vesicles are found in all eukaryotic cells. Particularly enriched in the brain, where they play a major role in the formation of neurotransmitter-containing pre-synaptic vesicles required for synaptic nerve transmission. Each clathrin protein molecule consists of three heavy chains and three light chains, joined together at the center to form a three-legged assembly called a triskelion.
22
23
ENDOCYTIC PATHWAY!
24
C. POTOCYTOSIS
Potocytosis is a type of receptor-mediated endocytosis in which small molecules are transported across the plasma membrane of a cell. The molecules are transported by caveolae(rather than clathrin-coated vesicles) and are deposited directly into the cytosol. The ligand is usually of low molecular mass(e.g. vitamins), but some larger molecules (such as lipids) can also act as ligands
25
D. WHAT IS MACROPINOCYTOSIS
Non-specific endocytosis of solute macromolecules. It has been exploited by some pathogenic bacteria as a novel route for entry into cells. Happens through actin-mediated membrane ruffling and blebbing.
26
3. WHAT IS APOPTOSIS?
27
Lysosomes can be used to kill cells when they are supposed to be destroyed. some cells have to die for proper development in an organism. ex: tadpole tail gets re-absorbed when it turns into a frog ex: loss of webbing between your fingers during fetal development
syndactyly
28
During fertilization, the lysosomal contents of the sperm are released outside, in order to digest the limiting membrane around the egg, thus facilitating the fusion of sperm and egg. Also helps in degradation of paternal(sperm) mitochondria.
29
The conditions of mechanical stress and pathogenic actions leads to the disruption of patches or formation of pores in the cell membrane. The secretory lysosomes fuses near to the damaged part of membrane and releases hydrolases outside the cell, among which a special hydrolase called acid sphingomyelinase causes the internalisation of the damaged patch. The fusion of the lysosome with the cell membrane provides extra lipids and prevents constriction of cellular boundary.
30
D. E. F.
Undisturbed cell A large disruption of plasma occurs The accumulating vesicles begin to fuse with one another to create large patch vesicles Vesicle-vesicle fusion creates more and larger patch vesicles A patch of internal membrane added is thereby added Post-resealing polymerization of F-actin and its contraction mediated by myosin restores subcortical network continuity. Resealing is now complete
31
Secretory lysosomes are a combination of conventional lysosomes and secretory granules. These secretory lysosomes package additional secretory products, respond to extracellular stimuli and fuse with the plasma membrane to release their contents. Secretory lysosomes are found, although not exclusively, in cells of the immune system and melanocytes.
32
KFERQ standing for lysine(K), phenylalanine (F), glutamate (E), arginine (R), and glutamine (Q) that cause the proteins bearing them to be selectively delivered to lysosomes for degradation. It is possible that the KFERQ sequences attach these proteins to cytosolic organelles that are on the way to being autophagocytosed, thereby dragging the proteins into the lysosome indirectly. Alternatively, there may be a specific transporter in the lysosomal membrane that recognizes these signals and transfers the proteins directly across the lysosomal membrane.
33
Material made of Silica: Rose quartz, glass, digital watches, porcelain, beach sand. Inhaled silica (silicon dioxide) dust enters lungs Macrophage ingest & silica dust enter secondary lysosomes Can't be digested; affects lysosome membrane integrity Lysis & release of enzymes Sets up inflammatory response in lung tissue Can lead to silicosis, tuberculosis, cancer and failure of respiratory system
34
35
36
37
38
39
40
TAY-SACHS DISEASE
It is an autosomal recessive disease which occurs due to deficiency of an enzyme called Hexosaminidase A (also called Nacetylglucosaminidase A). Occurrence in Jewish People of Ashkenazic (Central European) Descent Build up in secondary lysosomes and constrict nerve axons.
41
TAY-SACHS DISEASE
SYMPTOMS:
DIAGNOSIS:
cherry red spot on retina loss of peripheral vision reduction in development by age of 2 - seizures, diminishing mental functions loss of coordination Enzyme assay for measuring Hex-A activity.
42
GAUCHER DISORDER
It is genetically inherited autosomal recessive storage disorder, occurs due to the defiency of enzyme called glucocerebrosidase. A fatty substance known as glucocerebroside build up to toxic levels in the spleen, liver, lungs, bone marrow, and sometimes in the brain. 3 types: type 1,type 2, type 3 It is most prevalent in the Ashkenazi Jewish population (Jews of Eastern European ancestry).
43
GAUCHER DISORDER
SYMPTOMS: enlarged liver and spleen fatigue due to anemia low blood platelets bone pain bone deterioration and weakening (osteoporosis) lack of coordination (ataxia) brain damage, seizures DIAGNOSIS: Enzyme assay for measuring glucocerebrosidase (GC) activity. Genetic testing
44
NEIMANN-PICK DISORDER
This disease refers to a group of autosomal recessive inherited disorders known as leukodystrophies or lipid storage disorders in which certain fats accumulate in the tissues like the brain and liver and cause damage due to the defiency of Acid Sphingomyelinase (ASM). The four types of Niemann-Pick disease are commonly called Type A, Type B, Type C and Type D. Sometimes Type A and B are grouped together as Type I and C and D are grouped together as Type II. Certain group of population have high risk like: Ashkenazi Jewish population (Types A and B) French Canadian population of Nova Scotia (Type D)
45
NEIMANN-PICK DISORDER
SYMPTOMS:
DIAGNOSIS:
enlarged liver brain damage difficulty walking and swallowing increased sensitivity to touch difficulty speaking loss of muscle tone (hypotonia) learning difficulties
measuring the ASM activity in white blood cells. examining a skin sample (biopsy) for cholesterol storage.
46
POMPE DISEASE
Caused due to the lack of an enzyme called acid alpha-1,4glucosidase (also called acid maltase), thus called as glycogen storage disease or acid maltase deficiency. Leads to glycogen builds up in the body's cells and causes damage, mainly to muscles. 2 forms: Infantile form, Lateonset form.
47
POMPE DISEASE
SYMPTOMS: enlarged and weak heart muscle weakness respiratory difficulties DIAGNOSIS: Usually confused with multiple sclerosis. Enzyme assay for measuring acid alpha-glucosidase activity. in adults, a blood test can be used.
48
TREATMENT OF LSD'S
49
50
REFERENCES
Molecular biology of the cell, 5th edition Bruce Alberts et. al. Cell and molecular biology, 6th edition Karp Molecular cell biology, 5th edition Lodish et.al. Membrane dynamics and the biogenesis of lysosomes (Review) J. Paul Luzio, Viviane Poupon, Margaret R. Lindsay, Barbara M. Mullock, Robert C. Piper and Paul R. Pryor. Lysosome:- death by cell malfunction Danton H o'Neal. Lysosomes and mitochondria in the commitment to apoptosis: a potential role for cathepsin D and AIF. M Jattela, C Cande, G Kroemer
51
REFERENCES
52
THANK YOU...
53