Organelles

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Organelles
For this and the following lecture, the
corresponding text in Goodman is pp 101-134
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Relationships between organelles
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The Nucleus

• Nucleolus (arrow) site of rRNA transcription and
  processing and some aspects of ribosome assembly.
  The nucleolus is not membrane-bound, but is
  associated with regions of the chromosomes
  bearing genes for ribosomal RNAs.(arrows). These
  genes are present in multiple copies, and larger
  nucleoli are found in cells with high rates of
  protein synthesis.
• Euchromatin regions where DNA is decondensed and
  genes are being actively transcribed. This DNA
  does not stain darkly in an electron micrograph.
• Heterochromatin regions of highly condensed DNA
  not being transcribed. (arrowheads).

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Nature of the double membrane surrounding the
nucleus.
Nuclear pores link interior with cytoplasm
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The Inner Nuclear Membrane

• The inner nuclear membrane has integral proteins
  that anchor the nuclear lamina, a network of
  protein fibers to which chromatin is attached.

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Nuclear Lamina EM visualization of the network
just inside the inner nuclear membrane
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Lamins of network
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Isolated lamin B structure

• P, phosphorylation sites that regulate
  disassembly in mitosis
• Dimerization self-assembly of two proteins into
  functional unit
• Membrane and nuclear targeting regions (NLS
  nuclear localization sequence this allows the
  protein to return to the nucleus after it has
  been synthesized in the cytoplasm).
• Lamin B will attach to Lamin A

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Nuclear Lamina Diseases

• X-linked muscular dystrophy traced to mutations
  in a transmembrane protein still little
  understood, although the defective protein is
  identified. Different mutations in the same gene
  are causes for a lipodystrophy and a premature
  aging disease. The diverse effects and
  involvement of different tissues are as yet
  unexplained.

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Freeze Fracture Nuclear Pores
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Nuclear Pore Complexes
Each nuclear pore consists of eight subunits
surrounding a central aperture containing some
additional structures
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Transport through nuclear pores is passive (small
molecules) or energy-dependent (large molecules)
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Regulation of traffic through pores

• More than 1 million molecules/min. pass through
  3000-5000 nuclear pores of the typical cell.
• Outbound mRNA, tRNA, ribosomesproteins exported
  must bear a Nuclear Export Sequence)
• Inbound Nuclear and ribosomal proteins (which
  must bear a Nuclear Localization Sequence that
  makes it cargo. This is recognized by an
  adapter Importin that binds it to an import
  receptor)

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Nuclear business

• To store the DNA. Chromatin is DNA that is
  attached to the nuclear lamina in a condensed
  form associated with proteins (histones).
• To serve as the site for DNA transcription to RNA
  and processing of the RNA.
• In the nucleolus, ribosomes are assembled from
  gt40 proteins and 3 RNA molecules.
• Inbound traffic (through nuclear pores) includes
  proteins produced in the cytoplasm, including
  transcription factors and ribosomal proteins.
• Outbound traffic (through nuclear pores) includes
  Messenger RNAs and ribosomal subunits.
• All is cool until conditions inside and outside
  the cell trigger the chain of events leading to
  DNA replication and cell division..

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The outer nuclear membrane is continuous with the
Endoplasmic Reticulum (ER)
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ER Compartments

• Rough ER is studded with ribosomes and is
  specialized to support protein synthesis and
  protein sorting.
• Smooth ER is specialized for steroid synthesis,
  drug metabolism (the liver) or calcium storage
  (muscle).
• Transitional ER is where vesicles are budding off
  to carry cargo to the Golgi Apparatus.

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Differences in appearance of rough and smooth ER
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Golgi Apparatus

• Stacked membrane compartments that are polarized
  in cis) and out (trans). Illustration includes
  coated pre-Golgi intermediates and transitional
  elements.

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Golgi Functions

• Protein processing
• Lipid synthesis
• Distribution of proteins and lipids vesicles

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Lysosomes a specialized offspring of the Golgi
Apparatus that form when vesicles containing
lysosomal proteins fuse with endosomes that
result from endocytosis.
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Lysosomes are the dark bodies (arrows)
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Lysosomal function hydrolysis of material taken
up by endocytosis or phagocytosis and also to
recycle worn-out cell debris taken into endosomes
by a process called autophagy. The lysosomes are
acidified by a vacuolar-type H ATPase.
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Lysosomal Storage Diseases

• If a genetic defect leads to malfunction in one
  of the enzymes used by lysosomes to break down a
  particular class of substances, that substance
  will accumulate, i.e., be stored, in the
  lysosome. This accumulation leads to
  malfunction. In response, the cell produces more
  lysosomes and these also become clogged, and
  eventually the cell itself becomes dysfunctional.
  The tissues that produce the most of the
  unhydrolyzed material will be most affected.

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Gauchers Disease, the most common lysosomal
storage disease
The primary lesion of the disease is seen in
macrophages that ingest damaged leucocytes and
erythrocytes and then cannot digest their
membrane lipid. Ultimately this results in
symptoms that involve almost every organ system.
It is most common in people of Ashkenazi Jewish
lineage. Gauchers disease can be treated by IV
infusion of the missing enzyme. Unfortunately,
such treatments are quite expensive.
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Other Lysosomal Storage Diseases
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Peroxisomes

• Peroxisomes are membrane-bound organelles formed
  on the ER which then mature through accumulation
  of additional proteins (tailored to the needs of
  the cell) that are targeted to them from the
  cytoplasm.
• Fatty acid oxidation and other oxidative
  reactions, including breaking down uric acid,
  amino acids, purines and methanol occur in the
  controlled environment of the peroxisomes.
• Oxidative reactions that lead to the production
  of H2O2 occur in peroxisomes, but the potential
  toxicity of peroxide is managed by the presence
  of catalase, an antioxidant that decomposes H2O2
  and to water and O2 or uses the extra oxygen to
  oxidize another compound.

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Mitochondria

• Organelle believed to be derived from free-living
  bacterial-type ancestor.

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More obvious components of mitochondrial structure