Transcript Organelles

Organelles
For this and the following lecture, the
corresponding text in Goodman is pp 101-134
Relationships between organelles
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).
Nature of the double membrane surrounding the nucleus.
*Nuclear pores link
interior with
cytoplasm
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.
Nuclear Lamina: EM visualization of the network
just inside the inner nuclear membrane
Lamins of network
Isolated lamin B structure
•
•
•
•
P, phosphorylation sites
that regulate disassembly
in mitosis
Dimerization: selfassembly 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
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.
Freeze Fracture: Nuclear Pores
Nuclear Pore Complexes
Each nuclear pore
consists of eight
subunits
surrounding a
central aperture
containing some
additional
structures
Transport through nuclear pores is passive (small
molecules) or energy-dependent (large molecules)
Regulation of traffic through pores
• More than 1 million molecules/min. pass through
3000-5000 nuclear pores of the typical cell.
• Outbound: mRNA, tRNA, ribosomes…proteins
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)
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 >40
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…..
The outer nuclear membrane is continuous with the
Endoplasmic Reticulum (ER)
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.
Differences in appearance of rough
and smooth ER
Golgi Apparatus
• Stacked membrane compartments that are polarized: in
cis) and out (trans). Illustration includes coated preGolgi intermediates and transitional elements.
Golgi Functions
• Protein processing
• Lipid synthesis
• Distribution of proteins and lipids: vesicles
Lysosomes: a
specialized
offspring of the
Golgi Apparatus
that form when
vesicles
containing
lysosomal
proteins fuse with
endosomes that
result from
endocytosis.
Lysosomes are the dark bodies (arrows)
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.
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.
Gaucher’s 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. Gaucher’s
disease can be treated by
IV infusion of the missing
enzyme. Unfortunately,
such treatments are quite
expensive.
Other Lysosomal Storage Diseases
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.
Mitochondria
More obvious components of
mitochondrial structure
Where did organelles of eukaryotic cells come
from? Revisiting the origin of eukaryotic cells
• The Margulis Hypothesis: intracellular symbionts
became mitochondria, and perhaps other organelles
• Evidence:
– Mitochondria have bacterial-type chromosomes and the genes
are most closely related to bacterial ones
– Some mitochondrial genes are part of the nuclear DNA – this
could reflect the activity of mobile elements in the pre-eukaryotic
cells which had acquired symbionts
– Mitochondria have a double membrane – which could represent
a membrane-bound structure (bacterial cell) that got engulfed by
a host cell.
– In bacteria, a proton gradient across the plasma membrane is
used to phosphorylate ADP; in mitochondria, the same principle
operates across the inner mitochondrial membrane
Who were the host cells?
• Family tree analysis of genomes places the Archaea in
closer relationship to plants and animals than bacteria.
• So, the cells that took in the endosymbionts initially were
probably Archaea rather than bacteria.
• Archaea typically live in anaerobic environments, so it’s
probable that, initially, the endosymbionts offered
protection against the damaging effects of oxygen free
radicals, with ATP being a bonus that became available
only when the host cells began to express the carriers
that exchange ADP, ATP and phosphate across the
mitochondrial membranes.
Why do eukaryotic cells have a nucleus?
• “mobile elements” or transposons are
components of the genome that can cause
genes to move about within a genome
(“jumping genes”).
• With two different genomes within one cell,
transposons could create havoc by moving
genes randomly between the genomes. It
seems likely that the nuclear membrane
evolved as a defense against this.