4. Mitochondria-Cytoskeleton Flashcards
mitochondria stain__ and are __philic
there are numerous in which types of cells?
describe the structure of the outer, inner membranes, inter membrane space and the matrix
-what other events happen in these places
eosinophilic (acidophilic)
numerous in high energy cells
and cells that do ion transport ex: kidney lumen proximal convoluted tubules
outer membrane: smooth, this is where pyruvate and fatty acids enter mitochondria via the porin channels
-protein import receptors
intermembrane space: has cytochrome C – which when it is released, induces apoptosis
inner membrane: folded into cristae, impermeable to H+
and contains ATP synthase complex and ETC chain. again have here protein import receptors
matrix: many enzymes; this is where CCA yields ATP and NADH—> these go the ETC chain which helps move from matrix—> inter membrane space which come back to make ATP.
- matrix stores calcium and mitochrondrial DNA and ribosomes
peroxisomes? functions; complements what other organs? structure microscopy? genesis? where are the proteins made?
- spherical, membranous organelles containing enzymes (i.e. oxidase) that use o2 to remove H atoms from fatty acids—> this produces hydrogen peroxide
- complements Smooth ER and mitochondria bc: detox, metabolism of prescription drugs, and oxidation of long chain fatty acids
- catalase enzyme breaks down hydrogen peroxide to water and Ox
- staining shows dense central crystalloid aggregate of enzymes
genesis: budding from smooth ER or division of existing peroxisomes
proteins made on free ribosomes
what are diseases of peroxisomes?
zellweger syndrome:
autosomal recessive
mutation in genes invovled in peroxisome genesis OR protein import into peroxisomes
-so the long fatty acid chains accumulate and this affects several organs
what are the functions of microfilaments?
1) maintain cell shape
2) guides intracellular organelle trafficking
3) allows mechanical interactions with cell environment
what are the mechanical properties of microfilaments?
- microtubles easily deformed and easily rupture
- actin is more rigid and moderately resistant to strains
- intermediate filaments flexible and resistant to strain
functions of actin microfilament?
-resist tension
- cell shape
- cell migration
- cargo transport
- microvilli movement
- cytokinesis
- contraction
what are the monomers and polymers of acting? what is the structure? what about the ends?
what is needed for actin polymerization?
clinical significance?
minus end is the slow growing and is a pointed end
the plus end is fast growng and is a barbed end (claw)
-monomers are G acting and F is polymer
structure is double helix of 2 protofilaments with 7-8 nm diameter
-ATP hydrolyed to ADP weakens microfilament
need protein WASP which is important for nucleation of actin which is first step of polymerization. also need magnesium, potassium, and ATP
clinical: Wiskcott-Aldrich syndrome: x-linked recessive where wasp protein isn’t there to promote nucleation
s/s: TIE: thrombocytopenic (few platelets), infections, eczema
what is treadmilling
one end of the filament grows in length while the other end shrinks—> effect of moving toward the shrinking end
what is phalloidin
poison that binds and stabilizes F-actin
where do we find stable actin microfillaments?
1) muscle :
myosin and actin with actin being the thin filament
2) microvilli:
glycocalys: microvilli contain glycosaminoglycans and glycoproteins with actin as the central bundle
3) terminal web: base of microvilli with cross linkage to plasma membrane and to intermediate filaments
molecular component of focal adhesions
- fx
- components
function: connect ECM cells and resist stress
components: actin, integrin, fibronectin of ECM
-estonian love story
actin meats alpha actinin
they move with paxillin and vinculin on talon through integrin to connect to fibronectin
what is the motor protein for actin?
myosins–they transport vesicles on actin filaments
with ATP source
what is the motor protein for microtubles?
-which ways to they move?
kinesin and dynein—- move vesicles or other organelles with ATP source
kinesin is kind + end of microtubles and moves towards the periphery (kind people move away from negative people
dynein moves toward the center of the cell and is the - end (moves toward negative drama, circle group)
force for cytokinesis? components?
source of cytokinesis is a contractile ring made of actin and its motor protein myosin
what are the functions of microtubles?
- cell shape (like actin)
- mitosis chromosome separation
- cell migration (like actin)
- ciliary and flagellar movement
describe the assembly and disassembly of microtubles
what are the components of microtubles?
structure
shirnking vs growing end?
polymerization-depolymerization completed by exchanging GDP with GTP on the BETA tubulin monomer (GTP on alpha is just for structure and doesn’t hydrolyze)
- alpha and beta tubulin coponents - form heterodimers
shrinking: paused bc blunt ended microtuble intermediate generated by closure of terminal sheet structure
growing end: ‘cap’ of tubulin GTP subunits stabilize the microtuble lattice and conformation. cap is where new tubulin comes in
structure: 13 protofilaments
what/where are the structures of microtubules?
1) MT bundle:
2) axoneme : microtuble and dynein–> 9 special doublets microtubules. the doublet is 1 partial and 1 full mT in ring around center with 2 single microtubles
* dynein forms bridges btwn doublet microbutles
3) centriole: 9 triplets arranged turbine like; located near the nucleus and organize the mitotic spindle
then you find them in: cilia- axonemes centrosomes- centrioles basal body- centriole flagellum-axoneme
describe the structure of cilum
axoneme
basal body at base of the pairs
9 pairs of A and B microtubles joined by dynein
what are clinical indications of cilia?
defects in dynein- motor protein- leads to kartageners syndrome:
- immotile celia/sperm
- male and female infertility
- bronchiectasis
- sinusitis (baceria not pussed out)
- situs inversus association
so think: reproductive, lungs, and sinuses
microtubles associated proteins: how do they interact? clinical indications?
tau is a micrtubule associated protein (MAP) that forms intracellular aggregates
-can cause issues with alheimers disease if hyperphosphorylated
kinesisn or dynein motors move and encounter tau on the micrtubule tracks and are inhibited
- kinesin falls off
- dynein reverses its direction
what drugs affect microtubule stability?
vinblastine: binds free tubulin—> this inhibits formation of mitotic spindle. used in cancer therapy
taxol (paclitexal): binds microtubules, inhibits cell division. also cancer therapy
what are the 4 major families of intermediate filaments?
1) keratins: epithelial cells
2) vimentin-like family:
vimentin- mostly connective tissue
desmin- links myofibils in muscle
glial fibrillary acid protein in glia (GFAP)
3) neurofilaments- neurons
4) nuclear lamin- nuclear envelope of eukaryotic cells
describe the assembly of intermediate filaments
2 polypeptides wind around each other in coiled-coil structure
- dimers form tetramers which associate to form filaments
- have 8 filaments around each other in rope like structure
where do we find intermediate filaments
what are cadherins
desmosomes and hemidesmosomes
-both anchored to ECM
cadherins are calcium dependent adhesion molecules
what is epidermolysis bullosa
mutation ins keratin (intermediate micrfilament), or even in the laminin or autoimmune cause
s/s: slightest abrasion on skin would tear the epidermis from the underlying dermis. child has broad areas of dermis that were exposed. exposed dermis pretty much so you can’t control body temp, fluids, and infection
what are mallory bodies
what do they look like under microscope
seen in hepotocytes
-can have keratin filament accumulation in mallory bodies
these are eosinophilic
role of desmin
links myofibrils in muscle tissues
alheimers issues?
hyperphosphorylatin of tau and neurofilament s
what immunohistochemical stains would you use to investigate origin of tumors
what does positive look like?
antibodies against:
vimentin- mesenchymal tumors (mesynchaml cells derived from mesoderm)
desmin: smooth muscle tumor or skeletal tumor
keratin: epithelial tumors
GFAP: glia tumors
sarcomas leiomyosarcomas rhabdomyosarcomas carcinomas astrocytoma
positive: stain brwon
