Lecture 16 - Mitochondria in health and disease 1 Flashcards
mitochondrial DNA is closed…….., locted in the mitochondrial…… and there are multiple…… per cell
covalently, matrix, copies
how many protein encoding genes are there for mitochondrial DNA? what components to they all encode?
13, hydrophobic OXPHOS
how many rRNA and how many tRNAs does mitochondrial DNA have?
2 r, 22 t
name the 4 non-OXPHOS functions of mitochondria
apoptosis, cell growth, cell signalling, cell differentiation
name the 5 functions of mitochondria
metabolite transport, OXPHOS assembly, mitophagy, heme biosynthesis, protein import/sorting
name the 4 stages of aerobic respiration
glycolysis, Beta-oxidation, TCA cycle, OXPHOS,
name the products of the TCA/krebs cycle
2 carbon dioxide, 3 NADH, FADH2, GTP, 2H+, CoA
which 2 complexes carry out beta-oxidation of fatty acids?
complex 3 (CoQ) and complex 1
what is the name of complex 1?
NADH ubiquinone oxidoreductase
in complex 1:
1) …..electrons from NADH are transferred to chlorine
2) NADH is oxidised and ….. is reduced
3) FMN is oxidised as it passes electrons to ……
4) Fe-S is oxidised as it passes electrons to ………
5) H+ are pumped across the IMM by …..
1 - 2
2 - FMN
3 - Fe-S
4 - ubiquinone
5 - chlorine
in complex 1 how many H+ is there a net transfer of from matrix to IMS?
4
what is the name of complex 2?
succinate ubiquinone oxidoreductase or succinate dehydrogenase
in complex 2 what is the function of each subunit (SDHA,B,C,D)
SDHA = flavoprotein
B = Fe-S protein
C = cytochrome b560
D = cytochrome b
which 2 subunits of complex 2 are hydrophillic and in the matrix?
A, B
in complex 2, which 2 subunits are hydrophobic and integral membrane proteins?
C, D
complex 2 in the ETC catalyses the oxidation of succinate to what?
fumarate
in complex 2, electrons from FADH2 are transferred to ubiquinone via the Fe-S clusters in which subunit, reducing it to ubiquinol?
SDHB
what is the name of complex 3?
ubiquinol cytochrome c oxidoreductase
each monomer of complex 3 is made of how many polypeptide subunits?
11 each monomer
name the 4 active redox prosthetic groups in complex 3
2x b-type cytochromes (bL and bH)
cytochrome c1
rieske protein (Fe-S cluster)
the Q cycle in complex 3 results in:
- the oxidation of ubiquinol (QH2) to
……… (Q)
- the reduction of cytochrome c (cyt
c3+ to cyt c…….+)
- the concomitant transfer of four
protons into the intermembrane
space, via a two-cycle process
involving a ………
intermediate
ubiquinone, 2+, semiquinone
what is the name of complex 4?
cytochrome c oxidase
in complex 4, subunits 1-3 are …… encoded and subunits 4-13 are…… encoded
mtDNA, nuclear
complex 4 contains how many each of non-covalently bonded haem a and copper centres? what are they used for?
2 of each, for electron transfer
which haem a and which copper centre in complex 4 form a binuclear centre, binding to oxygen to reduce it?
CuB and cytochrome a3 (haem)
which complex in the ETC is the terminal electron acceptor, reducing oxygen to water and its reaction results in proton pumping?
complex 4
name the 2 domains of complex 5 (ATP synthase)
F0 and F1
which domain of complex 5/ATP synthase contain a proton channel?
F0
which domain of complex 5/ATP synthase contains C ring subunits?
F0
which domain of complex 5/ATP synthase contains additional subunits ATP6, ATP8, DAPIT?
F0
which domain of complex 5/ATP synthase contains 3alpha and 3beta subunits?
F1
which domain of complex 5/ATP synthase contains one gamma, one delta and one epsilon subunit, making up the central stalk?
F1
which domain of complex 5/ATP synthase contains subunits b, d, F6 and OSCP which make up the peripheral stalk?
F1
which domain of complex 5/ATP synthase contains an active site for ATP synthesis?
F1
which domain of complex 5/ATP synthase protrudes into the matrix and which domain is embedded in the inner membrane?
F1 protrudes
F0 embedded
which ring rotates first in ATP synthase, causing the gamma-apsilon central stalk to rotate? what does this result in in the 3xbeta subunits in the F1 domain enabling ADP +Pi = ATP?
C ring, results in conformational changes of the 3 beta subunits
true or false, OXPHOS is under dual genetic control?
true
name the 2 stands of mtDNA saying whether they are guanine rich or cytosine rich?
H strand is guanine rich
L strand is cytosine rich
approximately how many bp is human mtDNA? what % of the human genome does it account for roughly?
16,569bp, about 0.0006%
the non coding area of the mtDNA is known as what? which 2 functions occur in this region?
D loop, replication initiation and transcription initiation
what are the 4 genetic rules of mtDNA?
polyploid genome
heteroplasmy
threshold effect
maternal inheritance
why is the polyploid genome of mtDNA? what does it allow?
allows heteroplasmy and mtDNA inheritance
what is heteroplasmy of the mtDNA?
means the mtDNA genome has two or more variants = normal and mutated DNA copies
the threshold effect in mtDNA is when the number of …… mtDNA copies passes a threshold, meaning the ETC and …… fail
mutated, ATP synthesis
which 2 molecules detect cells with deleterious mtDNA mutations? what colour does each turn when this activity is detected?
cytochrome c oxidase (brown) and SDH (blue)
primary mtDNA disease is characterised by defective what?
OXPHOS
when can primary mtDNA disease present? is there a cure? is there a wide spectrum of clinical phenotypes?
can present at birth, childhood or adulthood. no cure. yes
