PFOS-015 CELLULAR ORGANELLES

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PFOS-015 CELLULAR ORGANELLES

• 1. Introduction
• 2. Nucleus
• 3. Endoplasmic reticulum
• 4. Golgi apparatus
• 5. Lysosomes
• 6. Mitochondria
• 7. Peroxisomes
• 8. Final Remarks

Prof. K.M. Chan Rm 513B, Basic Medical Science
Building Department of Biochemistry Chinese
University Tel [phone] Email
kingchan_at_cuhk.edu.hk
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1. Introduction

• Viruses and phage- show no cell membrane, their
  genetic materials either DNA or RNA are wrapped
  within the protein coat. They rely on cells to
  replicate.
• Cells prokaryotic cells, eukaryotic cells and
  archeons (archae bacteria)
• Biomolecules/chemicals wrapped inside membrane
  primitive cell
• Archaeon (Archaebacteria) found have ether-lipids
  with branched chains to live in high temperature
  vent by volcano outlet.
• Did life emerged from lava rock during volcano
  outbreak in the ocean to wrap up some useful
  chemical soap by chance?

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Membranes wrap the cells and their organelles
inside

• Membrane is a selectively permeable barrier
  between the cell and the external environment.
• The lipid bilayer structure defines inner
  membrane and outer membrane sides. Two sides of
  the membrane show different properties.
• Homeostasis- selective permeability allows the
  cell to maintain a constant internal environment.
• For eukaryotic cells, membranes also define
  cellular organelles to carry out different
  specific functions at a well defined location
  compartmentation.

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1.2 The E. coli. Cell and Human Cell

• A primitive cell like bacterium E .coli cell has
  a single compartment in which DNA, proteins,
  lipids and the biomolecules are crowded together
  in a well organized way.
• The cell is small, simple, it grows fast and can
  adapt to rapid environmental changes.
• In contrast, eukaryotic cells like human cells
  are a millions times larger, much more complex,
  and contain organelles to support different
  cellular functions from digestion to generation
  of energy and storage of nutrients.
• Human cells develop to specific cell types in
  different organs (differentiations). Specific
  cell types for specific functions.

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Size Range of Cells

• Small molecules (chemicals) lt 1 nm (10-9 m)
• Proteins and lipids- biomolecules lt 10 nm
• Ribosomes 20 nm viruses lt 100 nm
• Bacteria nm, 1 µm to 10 µm (10-6 m)
• Mitochondrion, 2 µm Nucleus, 7 µm
• Plant and animal cells 10-100 µm
• Frog egg, 2 mm salmon egg, 6 mm
• Chicken egg, 4-5 cm
• Length of muscle and nerve cells 50-70 cm.

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Bacterial cells have thick cell wall made of
carbohydrates, could be differentiated as Gram
and cells by Grams stain.
Mesosome is infolding of membrane for specialized
functions
Cell wall
Capsule
http//www.bact.wisc.edu/themicrobialworld/structu
re.html
Mesosome
Membrane
Nucleoid (DNA) region
Ribosomes
Peptidoglycan sugars plus amino acids
Contains lipo- polysaccharides (LPS) which are
endotoxins to animals in the outer membrane
Flagella
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May differentiate to different cell-types
Adapted from the Merck Manuals On-line Medical
Library http//www.merck.com/mmhe/sec01/ch001/ch0
01b.htmlsec01-ch001-ch001b-6
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2. The Nucleus

• Double membrane envelope outer membrane
  continues with endoplasmic reticulum.
• Nuclear pores to communicate with outside of the
  nucleus. Gates are necessary to ensure the
  various events impinging on gene transcription
  and cell signaling.
• Luminal subunits in between the outer and inner
  membrane with a ring structure and nuclear cage.
• Nucleolus contains chromatin actively transcribe
  ribosomal RNAs (rRNAs).

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Nuclear translocator protein (vehicle)
Architectures of nucleus
Pore complex
Outer membrane
Inner membrane
Luminal subunit
Chromatin DNA with histones and non-histone
proteins
Nuclear pores
Ribosome RNA translated to protein



Inner membrane

Outer Nuclear membrane

Rough Endoplasmic Reticulum

Nucleolus ribosomal RNA genes are being
transcribed to make ribosomal RNAs.

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3. Endoplasmic Reticulum (ER)

• Spans the entire cell.
• Attaches with numerous ribosomes for protein
  translation (Rough ER).
• The proteins made in the RER are folded, may be
  glycosylated (post-translational modifications by
  adding sugars), and sorted to various parts of
  the cell.
• ER also produces phospholipids (smooth ER).
• As a depot of calcium ions (smooth ER) in the
  cell for controlling the signaling of cellular
  processes.

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Rough ER dedicated for protein production
http//cellbio.utmb.edu/cellbio/ribosome.htmRibos
ome-Endoplasmic20Reticulum
From RER to Golgi Apparatus
http//cellbio.utmb.edu/cellbio/golgi.htm
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4. The Golgi Apparatus

• Proteins made in the RER are sorted to the Golgi
  apparatus for further processing.
• They enter the Golgi at the cis face from
  vesicles formed at the ends of the ER.
• In the cisternae of the Golgi, proteins are
  labeled (secondary modification), sorted and
  delivered to the trans face of the Golgi
  apparatus.

http//sun.menloschool.org/birchler/cells/animals
/golgi/structure.html
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Tunicamycin

• Proteins are glycosylated in ER before dispatch
  to the Golgi apparatus.
• It acts by mimicking the structure of
  UDP-N-acetylglucosamine, the substrate in the
  first enzymatic step in the glycosylation
  pathway.
• It thus blocks protein post-translational
  modification to kill eukaryotic cells
• Its an antibiotics.

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Protein sorting (trafficking)

• As vesicles formed in the Golgi, then sent to
  proper locations for specific function to be
  carried out in other parts of the cells (e.g.
  organelles or stored as secretory vesicles).
• Proteins in vesicles would accumulate and wait
  for signal to be exported out by exocytosis
  (either regulated or constitutively secreted out
  of the cells.
• Some proteins are delivered to and kept on cell
  membrane.

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Rough Endoplasmic Reticulum and Golgi Apparatus
Lysosome
Early endosome
Other organelles
Rough Endoplasmic Reticulum
Engulfed materials
Regulated secretary pathways
Vesicle
Trans Golgi apparatus
ECOSYTOSIS
Cis-Golgi apparatus
Constitutive secretary pathway
Golgi Apparatus
Proteins are further modified and sorted in the
Golgi apparatus
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5. The Lysosome

• A vesicle with acidic condition to digest and
  remove unwanted materials, or break down
  materials for cellular uptake or re-use.
• It contains digestive enzymes (primary lysosome).
• After bud off from the Golgi, the primary
  lysosomes fuse with autophagic vesicles to form
  phagocytic vacuoles (secondary lysosomes), or
  engulfed materials to form endosomes.
• Autophagy degradation of intracellular
  components in lysosomes heterophagy degradation
  of phagocytic materials (in-coming from outside).
• The debris could be discarded outside of the cell
  or kept as granules or recycle to cytoplasm.

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LYSOSOMAL HYDROLASES

• Synthesized in the ER, lysosomal hydrolases were
  moved to the cis Golgi network where they are
  covalently modified by the addition of
  Mannos-6-Phosphate (M6P)
• M6P receptor recognizes the labelled hydrolases
  in trans-Golgi and move them to the endosomes
• I-Cell disease is a genetic defect that produce
  the enzymes without M6P. Hence the enzymes could
  not be deposited to the endosomes for digestions.
• Glycosaminoglycans and glyco-lipids accumulated
  in the lysosomes (without proper digestions) and
  the patients exhibit psychomotor retardation and
  skeletal deformities. They die early, usually
  before age 8.

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Tay-Sachs Disease

• Its a lysosome storage disease
• lacks of hexosaminidase A.
• Results in the abnormal accumulation of other
  cellular materials in the brain.
• Mental retardation and blindness resulted from
  Ganglioside GM2 accumulation
• Also known as GM2 gangaliosidosis or
  Sphingolipidosis
• The lysosomes cannot function properly or even
  break to release not just digestive enzymes, but
  also acid in the cells to create a very acidic
  condition killing the neural cells.

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Gout and Rheumatoid Arthritis

• Gout is deposit of uric acid crystals of the
  joints often from over consumption of meat and
  Rheumatoid factor complexes in the leucocytes of
  the joints.
• Break lysosome to release enzymes that degrade
  the components of the synovial membrane,
  resulting in great pain and joint deformation.

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6. The MITOCHONDRION

• Double membrane of inner and outer.
• Inner membrane fold to create the matrix space
  and inter-membrane space in between inner and
  outer membrane.
• The matrix contains enzymes to oxidize
  metabolites.
• The inter-membrane has potential gradient
  generated by pumps at the inner membrane, energy
  released from the gradient produce ATP energy.

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Outer membrane, with channel forming proteins but
only permeable to 5 kDa molecules or less. Other
enzymes on this membrane facilitate metabolism of
lipid for use in matrix and transport of
specially required protein in the mitochondrion.
MAJOR FUNCTION OF MITOCHONDRION OXIDATIVE
PHOSPHORYLATION (oxidation of NADH to produce ATP)
Matrix, internal space with enzymes for oxidation
of pyruvate and fatty acids and for the citric
acid cycle (Krebs cycle).
Cristae in boxed region
Inner membrane, folded into numerous cristae to
increase total surface area for
electron-transport chain (respiratory enzymes),
ATP synthase and transporters for metabolites
going through the matrix.
Intermembrane space, for enzymes using ATP
passing out of the matrix to phosphorylate other
nucleotides.
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Mitochondrial (mt) disease

• Mt has its own DNA to make its own proteins with
  some imported proteins from cytoplasm
• Incorporated into eukaryotic cells by
  endosymbiotic processes during the course of
  evolution.
• Mt disease can arise from defective import of
  proteins (e.g. heat shock protein 70 needed for
  docking and folding of proteins in the mt) or
  mutations in mt genes.
• Tissues affected are those heavily dependent on
  ATP, e.g. nerve and muscle cells resulted in
  mental retardation and muscular weakness.
• For those need many mt (mt-gene) for function,
  Lebers hereditary optic neuropathy and
  Kearns-Sayre Syndrome are caused by mutation of
  NADH-CoQ reductase gene progressive blindness,
  abnormal heart beat and nerve degeneration
  resulted.

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7. Peroxisomes

• An organelle for oxidation of fatty acids and
  toxicants
• Abundant in hepatocytes (liver cells), where
  oxidation of fatty acids (and other organic
  matters) takes place and produces hydrogen
  peroxide
• Mainly produce catalase to decompose hydrogen
  peroxide into water.
• Zellweger syndrome is caused by the mistakes of
  protein import into the peroxisomes and hence
  accumulation of long chain fatty acids and
  pristanic acids in plasma and tissues.
• The defects can lead to severe impairment of many
  organs and death.

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8. Final Remarks

• Eukaryotic cells are highly organized with
  membranous organelle-as isolated compartments to
  carry out specific life processes and biological
  functions.
• The nucleus contains DNA for gene transcription
  and production of RNAs. Transcriptional factors
  and signals go in and out through nuclear pores
  under a tight control.
• Rough ER handles translation and
  post-translational modification, protein sorting,
  vesicle formation are done in Golgi apparatus.
• Mitochondiron is responsible for respiration and
  ATP energy production it has 2 membranes and its
  own genes.
• Lysosomes are for cellular digestions,
  peroxisomes are for fatty acid oxidation and
  detoxification or Redox reactions of intoxicated
  chemicals.