Cellular organization Flashcards
What are the components of the cell nucleus
- nuclear envelope
- nuclear lamina
- nuclear pores
- nucleolus
- nucleoplasm
Nuclear envelope
Inner nuclear membrane:
- faces nucleoplasm
- in contact with nuclear lamina
Outer nuclear membrane:
- faces cytoplasm
- continuous with ER
- cytoplasmic surface contains ribosomes (rER)
Nuclear lamina
Thin, sheet-like meshwork beneath the inner nuclear membrane
- Has nuclear lamins– type of intermediate filamant, lamin A & B
- Scaffold for nuclear envelope, chromatin, & nuclear pores. Disassembles during mitosis
Nuclear pore complex (NPC)
- Span inner and outer nuclear membranes
- Made up of more >50 proteins– nucleoporins
- 3000-4000 NPC’s in a typical nuclear envelope
- Allow transport of molecules bw nucleus and cytoplasm (moles <9 nm diffuse freely through the pore, >9 nm needs active transport)
Nucleolus
-Site of ribosomal production: rRNA is transcribed, ribosomal subunits are assembled
-3 zones
1- Fibrillar center (FC)- pale staining region. DNA loops of 5 chromosomes - contain rRNA genes
2- Fibrillar material (F) - transcription of rRNA genes
3- Granular material (G)- initial ribosomal assembly
Nucleosome
Fundamental structural unit of chromatin
- Macromolecular complex: 8 histone molecules (octamer), 2 loops of DNA wrap around core octomer, “beads on a string”
- In both euchromatin and heterochromatin
Centromere
- centric heterochromatin
- persists throughout interphase
- constructed region that holds sister chromatids together
- Also site of kinetochore formation
Telomere
- At ends of chromosomes
- Repeated seqs that allow the ends of the chromosomes to be replicated.
Chromosome structure contains:
- Specialized NT sequences – bind specific proteins for replication and segregation
- Telomere
- Centromere
- Replication origin
Polyribosome
Many ribosomes bound to a single mRNA molec (more than 1 ribosome translating a single message)
2 types of ribosomes
membrane bound and free
Membrane bound ribosome synthesizes proteins that go …
Attached to cytoplasmic surface of ER membrane (RER). They translate the message synthesizing proteins that are being translocated to the ER lumen, and then to golgi. From the golgi there are 3 possible destinations: lysosome, secretion (default), plasma membrane
Free ribosomes path synthesizes proteins that go…
Nucleus, mitochondria, cytosol (default), peroxisomes
ER general characteristics
- interconnected network of branching tubules & flattened sacs distributed throughout the cytoplasm
- At certain sites, ER membrane is continuous with outer nuclear membrane
- Two regions- smooth (synth of lipids & detox), rough (synth of proteins destined for plasma membrane, lysosomes, or secretion)
Smooth ER
- Abundant in cells specialized in lipid metabolism – well developed in cells that synth and secrete steroids
- Plays major role in detox: ex hepatocytes & detoxifying enzymes – CYTOCHROME P450 SYSTEM
- Also functions to sequester Ca2+ – ex muscle cells and sarcoplasmic reticulum
- More tubular and not as flat as RER
Golgi general characteristics
- Complex of flattened, membrane enclosed cisternae
- Usually located next to nucleus and centrosome (location is microtubule dependent)
- Each golgi stack has 2 faces: cis (entry, faces toward nucleus) (contains CGN), trans (exit, faces out, from trans go to apical surface) (contains TGN)
- well developed in secretory cells– plasma cells (secrete antibodies), pancreatic acinar cells (secrete digestive enzymes)
What mediates bidirectional traffic bw ER and golgi?
coatomer-coated vesicles: COP-I and COP-II
COP-I coated vesicles
RETROGRADE transport (cis golgi network–> rER)
COP-II coated vesicles
ANTEROGRAE transport
-carry newly synthesized proteins from rER to CGN
Golgi specific functions
1- Post-translational mods:
- glycosylation
- sulfation
- phosphorylation
- proteolysis
2-sorting & 3-packing, both when they get to TGN
Vesicular trafficking pathways from golgi
1- constitutive secretory pathway - vesicles produced for continuous secretion
2-regulated secretory pathway - vesicles are stored and secreted with stim
3- lysosomal pathway (use endosomes)
Lysosome characteristics
- digestive organelles – function in controlled intracellular digestion of macromolecules
- membrane-enclosed compartments filled with ~40 types of hydrolytic enzymes: acid hydrolases, req acidic pH
Secondary lysosome
- phagolysosome
- stains with darker patches than lysosome
How do we get proteins that were synth in ER and shuttled to golgi specifically to lysosomes (targeting proteins to lysosomes)?
- Precursor lysosomal hydrolases are covalently modified by addition of mannose 6-phosphate (M6P) in golgi
- M6P receptor in TGN recognized lysosomal enzymes for transport to lysosomes
Lysosomal storage diseases (LSDs)
- dysfunctional lysosomes
- > 40 (LSDs)
- 1:7000 live births
- result from mutations in genes that encode lysosomal enzymes
Results in:
- accumulation of undigested products
- disruption of normal cell function
- cell death
Tay-Sachs Disease
- First lysosomal storage disease (LSD)
- Deficiency of HEXA – beta-hexosaminidase A, alpha subunit
- Gene location: chrom 15q24.1
- Result in accumulation of GM2 ganglioside (bc can’t break it down)
- Death of neurons in brain and spinal cord
3 pathways to lysosome digestion (name)
1- phagocytosis
2- endocytosis
3- autophagy
Autophagy (characteristics and process)
- Major cellular pathway to degrade proteins & organelles in lysosome
- “self-eating”
- Essential role in starvation, cellular differentiation, cell death and aging
process:
- Intracellular membrane surrounds the organelle and cytoplasm
- Autophagosome formed – (double membrane vacuole
- Fusion of autophagosome with lysosome
- Contents are degraded, recycled, and reused
Proteasome
- Proteasome-mediated protein degradation:
- Large protein complex
- ATP dep
- DESTROYS PROTEINS W/O INVOLVING LYSOSOMES
- Polyubiquitination: Proteins targeted for destruction are covalently tagged with the UBIQUITIN protein
- Destruction of abnormal proteins & normal short-lived regulatory proteins – ex cyclinc, TFs, tumorsuppressors
- Proteasome inhs are used as anti-cancer agents
What are inclusions? Name them
Cytoplasmic or nuclear xtures formed from metabolic products of the cell
Pigments:
MEMBRANE BOUND
1. Lipofucsin – brownish-gold pigment, seen in non-dividing cells (accumulated over years, “WEAR & TEAR” PIGMENT). Conglomerate of lipids, metals, organic molecs
2. Hemosiderrin
3. Melanin
NON MEMBRANE BOUND
-glycogen– TEM dense bodies. Storage form of glucose (catabolism releases glu for E)
-Lipid– TEM dense. Fat droplets (spherical droplets of triglyceride, liquid at body temp). Energy store and source of short C chains for membr synth. LIPID STORAGE DISEASES (LIPIDOSES) – lipid droplets accumulate in abnormal amounts or locations
List parts of the mt
- Inner membrane
- Matrix
- Outer membrane
- Intermembrane space
Inner membrane of mt
-thinner and thrown into folds
3 major functions:
- oxidation rxns– ETC
- Synth ATP – ATP synthase
- Regulate metabolite transport into and out of the matrix
Mt matrix
- Mixture of hundreds of enzymes –citric acid cycle, ox pyruvate and FAs
- Matrix granules– store Calcium
- Mito DNA, ribosomes, and tRNA
Outer membrane of mt
-contains PORINS – large channel forming proteins (allows free passage of small molecs)
Intermembrane space of mt
- space bw inner and outer membr
- contain specific enzymes that use ATP generated by the inner membrane
- CTYOCHROME C – IMPT FACTOR IN INTRINIC APOPTOSIS PATHWAY
Mitochondria diseases
- Results in defects in mito enzymes req for ATP production –dysfunctional mito respiratory chain
- Affect tissues that req large amts of ATP – Neurons & muscle cells
Myoclinic epilepsy with ragged red fibers (MERRF)
mitochondrial disease
- mutation in a tRNA gene
- MT-TK
Leber hereditary optic neuropathy
mitochondrial disease
-mutations in MT-ND1, ND4, ND4L, ND6 genes
Peroxisomes
- impt role in fat metabolism. VERY LONG CHAIN FATTY ACID (VLCFA) beta-oxidation. catalyze initial rxns in formation of plasmalogens
- peroxisomal proteins synth by FREE (CYTOPLASMIC) RIBOSOMES
- peroxisomal diseases – dysfunctional peroxisomes, ZELLWEGER SYNDROME
Zellweger syndrome
peroxisomal disease - mutations in genes req for peroxisome function, defective import of peroxisomal proteins
