Exam 2 Flashcards
mitochondria structure
double membrane system:
outer membrane,
inner membrane,
intermembrane space,
matrix
mitochondria outer membrane
contains porins (channels highly permeable to small molecules and ions)
mitochondria inner membrane
cristae, many proteins for oxidative metabolism and metabolite transport
mitochondria matrix
contains mtDNA and metabolism enzymes
mitochondria organization
more mitos in high demand tissues and locations, make up dynamic tubular network (fission and fusion)
mitochondria fission
division into two units;
cell growth and division, cell polarity, eliminating bad mitos
mitochondria fusion
merging of two or more mitos inner and outer membranes;
increase energy production, buffering bad mitos, alleviating oxidative damage
mitochondria oxidative metabolism of ___
pyruvate, FAs, and AAs
mitochondria oxidative metabolism processes
TCA/CAC/Krebs,
oxidative phosphorylation
mitochondria TCA/CAC/Krebs
in matrix;
pyruvate/FAs to acetyl CoA to CO2;
NAD+ and FAD reduced to NADH and FADH2 (carry electrons)
mitochondria oxidative phosphorylation
cristae of inner membrane;
energy releasing reactions coupled to energy requiring reactions;
NADH and FADH2;
ATP synthase
mitochondria oxidative phosphorylation energy releasing reactions
electron donors to electron acceptors
mitochondria oxidative phosphorylation energy requiring reactions
ADP to ATP
mitochondria oxidative phosphorylation NADH and FADH2
NADH and FADH2 to complex I and II, to III, to IV, to O2;
exergonic (to O2);
released energy drives pumps I, III, IV to pump into intermembrane space creating potential energy as proton gradient
mitochondria oxidative phosphorylation NADH
mitochondria oxidative phosphorylation FADH2
TCA/CAC/Krebs metabolites
for growth and cell signaling;
used by mito and cytosolic proteins to form nucleotides, AAs, and FAs and cholesterol; also control gene expression by chromatin and post-translational modifications
mitochondria genetics
circular dsDNA in nucleoid, polyploid (heteroplasmy), replicate independent from cell division
heteroplasmy
two or more mtDNA variants exist in same cell
mitochondria post-translational protein import
majority of mito proteins translated by free ribosomes
mitochondria post-translational protein import Tom
outer membrane translocase;
translocate N-terminal presequence and internal sequence containing polypeptides;
send to intermembrane space
mitochondria post-translational protein import Tim 23
inner membrane translocase;
translocate N-terminal presequence containing polypeptides into matrix or inner membrane;
PAM (import motor), MPP (snips presequence), membrane potential, ATP to ADP
mitochondria post-translational protein import Tim 22
inner membrane translocase;
translocate internal sequence containing polypeptides bound to chaperones to inner membrane
mitochondria post-translational protein import Tim 22 chaperones
Tim 9 and 10 help stabilize hydrophobic regions of polypeptides going through intermembrane space (Tom to Tim 22 or SAM) (intermembrane space is aqueous like cytosol)
mitochondria post-translational protein import Oxa 1 translocase
inner membrane translocase;
for proteins translated inside mitochondria
mitochondria post-translational protein import Mim 1
outer membrane translocase;
import α helix integral outer membrane proteins;
cytoplasm to Mim 1 to laterally transported into outer membrane
mitochondria post-translational protein import SAM complex
outer membrane translocase;
import ß-barrel integral outer membrane proteins;
cytoplasm to Tom to intermembrane space to SAM complex to lateral transport into outer membrane
mitochondrial disease
many syndromes/age of onset/severity of diseases;
inherited pathological mutations (in mom, every tissue);
sporadic pathological mutations (not every tissue);
onset/severity depends on level of heteroplasmy (how much mutant vs mtDNA);
replacement therapy
peroxisome structure
single membrane;
dynamic size, number, morphology, and function
peroxisome function
major metabolic organelles;
1) lipid synthesis
2) FA oxidation
3) ROS metabolism
peroxisome function lipid synthesis
lipids including plasmalogens;
R1 and R2 are fatty acid tails;
enriched in membranes of brain, cardiac, immune tissues
peroxisome function FA oxidation
in peroxisome: fatty acids activated to acyl-CoA shortened to acetyl CoA to acetyl-carnitine;
transferred to mito as acetyl-carnitine;
in mito: acetyl-carnitine to acetyl CoA to Krebs cycle oxidation to CO2
peroxisome function ROS (reactive oxygen species) metabolism
cellular metabolism increases ROS which can cause oxidative damage to macromolecules;
ROS metabolizing enzymes decreases ROS levels (such as catalase and SOD)
peroxisome biogenesis types
de novo (brand new),
division (making new from old)
peroxisome biogenesis de novo
ER vesicles bud with PEX transmembrane proteins;
cytosolic-derived matrix proteins
peroxisome biogenesis de novo transmembrane proteins
V1 vesicle and V2 vesicle (diff PEX proteins) fuse to form peroxisome membrane
peroxisome biogenesis de novo matrix proteins
cytosol PEXs recognize peroxisome targeting sequences (on polypeptide) then mediate docking and translocation into peroxisome
peroxisome biogenesis division
ER vesicles bud and fuse with peroxisome to grow membrane and add more proteins;
peroxisome divides
peroxisome disorders
diverse but often very severe,
mutations in peroxisome genes (like metabolic enzymes and PEX proteins)
cytoskeleton
network of protein filaments plus proteins
actin filament structure
actin monomers (G actin) and actin filaments (F actin)
actin monomers
G (globular) actin;
head to tail interactions
actin filaments
F (filamentous) actin;
polymers of G actin (dimerize then trimerize then filament);
distinct polarity, plus (barbed) and minus (pointed) end
actin filament assembly
nucleation, elongation (unbranched), and steady-state (tread milling)
actin filament assembly nucleation
profilin activates G actin monomers;
nucleators stabilize first actin dimer and promote elongation at + end
actin filament assembly nucleation profilin
binds to actin and activates with ATP so it polymerizes better;
ADP to ATP
actin filament assembly nucleation nucleators
formin dimer for unbranched, Arp2/3 for branched
actin filament assembly elongation (unbranched)
profilin/ATP bound actin binds at + end of formin dimer;
actin acts as ATPase
actin filament assembly elongation (unbranched) actin as ATPase
hydrolysis (ATP to ADP) is activated when actin is incorporated into the filament, ADP-actin dissociates more readily
actin filament assembly steady-state/tread milling
ATP-actin joins + end at the same rate that ADP-actin leaves the - end;
filament length maintenance
actin filament organization is maintained by
capping proteins, filament stabilizing proteins (tropomyosin),
cross linking proteins
actin filament organization capping proteins and filament stabilizing proteins
maintain actin filament length
actin filament organization cross linking proteins
organize actin bundles (parallel arrays, microvilli) and actin networks (orthogonal arrays) between adjacent actin filaments
actin at the edge
cytoskeletal proteins and cell cortex
cytoskeletal proteins
link actin to plasma membrane;
spectrin and ankyrin
cytoskeletal protein spectrin
binds actin filaments and phospholipids
cytoskeletal protein ankyrin
bind spectrin and transmembrane proteins
cell cortex
protein + membrane edge of the cell; coordinates shape, movement, interaction with other cells or environment
myosin structure and function
coordinates the activities of actin;
prototype molecular motor;
dimer;
coiled coil tail groups;
globular head groups contain all functional domains
myosin:
prototype molecular motor
most myosins walk from - to + end of F actin using ATP;
chemical (ATP) to mechanical (walk) energy
myosin:
globular head groups functional domains
actin binding;
ATP binding;
lever arm
myosin II mechanism with actin:
starting position
after previous round, myosin attached to actin but not bound to ATP
myosin II mechanism with actin:
ATP
ATP binding,
changes head group structure,
actin dissociation/cocking of lever arm,
ATP hydrolysis,
ADP + Pi bound,
contact with actin further toward plus end
myosin II mechanism with actin:
power stroke
Pi released,
ADP released,
myosin head returns to uncocked position
actin-myosin in muscle contraction:
myofibrils
rod-like organelles in cytoplasm of muscle fibers (cells);
repeated sections of sarcomeres between two Z discs
actin-myosin in muscle contraction:
A band
thick filaments of myosin overlapping with actin;
myosin anchored at M line
actin-myosin in muscle contraction:
I band
only thin filaments of F actin;
plus end anchored to Z disc
actin-myosin in muscle contraction:
sliding filament model
sarcomeres shorten, bringing Z discs closer;
myosin orientation reverses at M line;
titin springs hold myosin in place
actin-myosin in muscle contraction:
regulation of contraction by Ca2+
nerve sends action potential,
travels through T-tubules of sarcolemma,
Ca2+ release from sarcoplasmic reticulum,
binds to troponin bound to tropomyosin which is moved
reveals myosin binding sites where myosin head can bind actin
actin-myosin in cytokinesis:
contractile ring
constricts plasma membrane in two
actin-myosin in cytokinesis:
regulation of contraction
Ca2+ binds calmodulin causing shape change;
calmodulin binds to MLCK;
MLCK activates myosin II with Pi
microtubule structure smallest unit
heterodimer of α and β tubulin;
each encoded by small family of genes;
both bind GTP in dimer form;
β has GTPase activity;
α stimulates β GTPase activity
microtubule structure polymer
made up of tubulin heterodimers;
protofilaments, long strands of dimers arranged in parallel;
centrosome assembles 10-15 protofilaments around hollow core and stabilizes - end;
distinct polarity, - end is α, + end is β
microtubule assembly and disassembly
GTP dimers bind at + end;
GTPase activity;
dynamic instability at + end;
microtubule associated proteins (MAPs)
microtubule assembly and disassembly:
GTPase activity
when dimers polymerized hydrolysis is activated;
GDP bound tubulin dissociates more readily
microtubule assembly and disassembly:
dynamic instability
catastrophe and regrowth at the + end
microtubule assembly and disassembly:
MAPs
microtubule associated proteins (MAPs) regulate + end stability;
polymerase accelerates growth;
depolymerase promotes shrinkage;
CLASP stops shrinkage
microtubule growth
when GTP-dimer addition exceeds hydrolysis (GDP-dimer formation)
microtubule shrinkage (catastrophe)
when hydrolysis (GDP-dimer formation) exceeds GTP-dimer formation
microtubule regrowth (rescue)
when GDP-dimer leaving is stopped allowing GTP-dimer cap formation
microtubule organization in prototypical animal cell
microtubules grow and extend from microtubule organizing center (MTOC)
microtubule organizing center (MTOC) in animal cells
centrosome;
pair of centrioles at center;
pericentriolar material
MTOC in animals pair of centrioles
9 triplets of microtubules arranged in wheel structure
MTOC in animals pericentriolar material
matrix of proteins surrounding centrioles;
γ tubulin (gamma) initiates microtubule polymerization;
microtubule anchoring proteins hold - ends
microtubules in neuron
determine polarity;
stable microtubules in axons and dendrites;
ends terminate in cytoplasm (not MTOC)
stable microtubules in neuron
transport of cargo to the processes;
retrograde transport of signals to the cell body (nucleus)
ends of microtubules in neuron
terminate in cytoplasm (not MTOC);
capped and stabilized by MAPs (MAP1, MAP2, tau);
distinct orientation in each process
orientation of ends of microtubules in neuron
dendrites polymerize in both directions (+ and - ends both terminate in cytoplasm);
axons polymerize anterograde (- ends terminate in cytoplasm)
microtubular motor proteins
walk along stable microtubules;
two families kinesins and dyneins;
homodimers with heavy and light chains
microtubular motor proteins:
kinesins
move toward + end;
carry vesicles anterograde in cell endocytic and secretory pathways
microtubular motor proteins:
dyneins
move toward - end;
carry vesicles retrograde in cell endocytic and secretory pathways
microtubular motor proteins:
heavy chains
ATPase activity and tubulin binding;
hydrolysis changes conformation causing movement
microtubular motor proteins:
light chains
carry cargo
microtubule intracellular organization and transport
microtubule - ends located near nucleus/cell interior;
transport of vesicles in endocytic and secretory pathways (kinesins anterograde, dyneins retrograde);
without microtubules ER would collapse and gogli unstacking
