1.Membrane-limited organelles 2.Golgi apparatus 3...
Transcript of 1.Membrane-limited organelles 2.Golgi apparatus 3...
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Membranous Organelles 2
1. Membrane-limited organelles
2. Golgi apparatus
3. Lysosomes
4. Peroxisomes (microbodies)
5. Secretory vesicles (granules)
6. Coated vesicles
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Prof. Dr. Nikolai Lazarov
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Membrane-limited organelles
� Endoplasmic reticulum
� Annulate lamellae
� Mitochondria
� Golgi apparatus
� Lysosomes
� Proteasomes
� Secretory vesicles
� Transport vesicles
� Peroxisomes
� Coated vesicles
� Nucleus
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sorting
Golgi Apparatus
Membranous Organelles
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Golgi Apparatus
� ital. – apparato reticolare interno:
Cammillo Golgi, 1886, 1898
� Synonyms:� Golgi complex
� Golgi zone
� Golgi bodies
� Ultrastructure: A. Dalton, M. Felix, 1953
Dictyosome:
� stacks of smooth membrane-limited:
� 3-12 flattened cisternae (50-200 nm)
� vesicles (30-50 nm)
� large, clear vacuoles (200-300 nm)
Cammillo Golgi
(1843-1926)
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Golgi Apparatus – structure
� both morphologically and functionally polarized structure:
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Golgi Apparatus –internal polarity
GERL concept – zone of Novikoff (1964)
G – Golgi apparatus
ER – Endoplasmic Reticulum
L – Lysosomes
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Golgi Apparatus –functional polarity
� glycosylation, sulfation, phosphorylation,
and limited proteolysis of proteins
� initiates packing,
concentration, and storage
of secretory products
� trafficking and sorting of proteins:
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Golgi Apparatus –clinical relevance
� Hyperproinsulinaemia:
� Mucolipidosis – a group of inherited metabolic disorders in which mucopolysaccharides and lipids accumulate in tissues:� type I (sialidosis) – a deficiency of
the lysosomal enzyme sialidase
� type II (inclusion, I-cell disease) - a deficiency in a phosphorylating enzyme normally present in the Golgi complex � lysosomes contain large inclusions of undigested glycosaminoglycans and glycolipids
� type III (pseudo-Hurler polydystrophy)– the glycoproteins are not destined for lysosomes
� type IV – alterations of a protein in the cell that is believed to be involved in the movement of molecules such as calcium across cell membranes
�immature forms of insulin make up the majority of circulating insulin
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intracellulardigestion
Lysosomes
Membranous Organelles
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Lysosomes
� Discovered by Christian de Duve, 1955
Spherical organelles:
Christian de Duve
(1917-2013)
� (Gr. lysis, dissolution or destruction + soma, body)
� size – 0.05-0.5 μm
� single layer (unit) membrane – 6 nm
� lysosomal matrix – pH 5 � favorable for enzymatic activity
� more than 40 hydrolytic enzymes
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Lysosomes – stages
� Primary lysosomes:
inactive enzymes
� Secondary lysosomes
(phagosomes, phagolysosomes):
� heterolysosomes
(heterophagosomes)
� autophagosomes
(autophagic vacuoles)
� residual bodies
(telolysosomes)
� lipofuscin droplets
� pinocytotic vesicles
� multivesicular bodies
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Lysosomes – ultrastructure
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Lysosomes –"suicide-bags" or "suicide-sacs"
� autophagic cell death – a form of programmed self destruction
(autolysis)
� (autophagy – self digestion, Gr. auto, self + phagein, to eat)
� the cells' garbage disposal system
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Prof. Dr. Nikolai Lazarov
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Proteasomes
� There are two major intracellular devices in which damaged or unneeded proteins are broken down:
� lysosomes
� proteasomes
� Proteasomes deal primarily with proteins as individual molecules, whereas lysosomes digest bulk material introduced into the cell or whole organelles and vesicles
� Proteasome has:
� multiple-protease complexes that digest proteins targeted
NB: The 2004 Nobel Prize in Chemistry was awarded to Aaron Ciechanover, Avram Hershko
and Irwin Rose ""for the discovery of ubiquitin-mediated protein degradation"
� a core particle with the shape of a barrel� a regulatory particle that contains ATPase
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Lysosomes –clinical relevance
� Lysosomal storage diseases:
Phillippe Gaucher
(1854-1918)
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sites foroxygen
utilization
Peroxisomes
Membranous Organelles
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� Gr. peroxide + soma, body� microbodies: Rhodin, 1954
Peroxisomes (microbodies)
Spherical organelles: 70-100/cell
� size – 0.5-3 μm (macroperoxisomes)� microperoxisomes – 0.1-0.3 μm
� homogeneous matrix(crystalloid core or nucleoid)
� marginal plate� single layer membrane – 6-8 nm
� identified by EM as organelles by Christian de Duve, 1967
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Peroxisomes –structure and function
� Functions:
� a compartment for oxidation reactions:
� decomposes H2O2 to H2O and O2 and eliminates it
� degrades several toxic molecules and prescription drugs
� involved in lipid biosynthesis
� important role in cellular respiration
� Enzymes: >50
�catalase – 40%
�peroxidase
�β-oxydase of very long-chain fatty acids
�D- and L-amino oxydases
�urate oxidase
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Sigvald Bernhard Refsum
(1907–1991)
Peroxisomes –clinical relevance
� Peroxisomal disorders –17 inherited metabolic diseases:
�Refsum's disease – leukodystrophy:�faulty enzymes during the alpha-oxidation of
phytanic acid
�Zellweger syndrome:�deficiency in the protein import can lead to empty peroxisomes
�X-chromosome-linked adrenoleukodystrophy:�a defective integral membrane protein that participates in transporting very long-chain fatty acids into the peroxisome for β-oxidation
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Проф. д-р Николай Лазаров
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� Von Gierke disease:�glycogen storage disease type 1�impairment of glycogenolysis:
�hypoglycemia�hyperlipidemia (excess acetyl CoA) �accumulation of glycogen in the liver and kidneys
Peroxisomes –clinical relevance
Edgar Otto Conrad von Gierke
(1877–1945)
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storage and release of secretory products
Secretory vesicles(granules)
Membranous Organelles
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Zymogen granules – digestive enzymes
Secretory vesicles
� Secretory granules:� shape – spherical
� diameter – 0.15 µm->1 µm
� clathrin-coated vesicles
� core – histamine, chromogranin В, secretogranin ІІ
Neurosecretosomes – hormones
Synaptic vesicles – transmitters
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Secretory vesicles
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Coated vesicles
E.G. Gray, 1962 – coated vesicles
�size – 20-250 nm
�6-8 nm spines
�single membrane – 7.5-8 nm
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� 3 types coated vesicles:� clathrin-coated vesicles – 6-8 nm spines
� coatomer-coated vesicles� caveolae
Coated vesicles – types
"for their discoveries of machinery regulating vesicle
traffic, a major transport system in our cells".
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Clathrin-coated vesicles
Clathrin-coated pits and vesicles
� mediate selective transport of transmembrane receptors
� transmembrane proteins(spines) 6-8 nm
� clathrin molecules, bound via adaptin
� formed by endocytosis or from the Golgi apparatus
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Coatomer-coated vesicles
� COPII (α-COP) – responsible for anterograde transport from the endoplasmic reticulum to the Golgi complex
� COPI (β-COP) – involved in Golgi to endoplasmic reticulum (retrograde)
vesicle transport, and possibly also in intra-Golgi transport
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Caveolae
�potocytosis – a type of
receptor-mediated endocytosis
� Lat. for little caves �small (50–100 nm) invaginations of the plasma membrane
�in endothelial cells and adipocytes
�completely lack in neurons
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Thank you…