Lecture 16 - Mitochondria in health and disease 1

Question 1

mitochondrial DNA is closed…….., locted in the mitochondrial…… and there are multiple…… per cell

Answer 1

covalently, matrix, copies

Question 2

how many protein encoding genes are there for mitochondrial DNA? what components to they all encode?

Answer 2

13, hydrophobic OXPHOS

Question 3

how many rRNA and how many tRNAs does mitochondrial DNA have?

Answer 3

2 r, 22 t

Question 4

name the 4 non-OXPHOS functions of mitochondria

Answer 4

apoptosis, cell growth, cell signalling, cell differentiation

Question 5

name the 5 functions of mitochondria

Answer 5

metabolite transport, OXPHOS assembly, mitophagy, heme biosynthesis, protein import/sorting

Question 6

name the 4 stages of aerobic respiration

Answer 6

glycolysis, Beta-oxidation, TCA cycle, OXPHOS,

Question 7

name the products of the TCA/krebs cycle

Answer 7

2 carbon dioxide, 3 NADH, FADH2, GTP, 2H+, CoA

Question 8

which 2 complexes carry out beta-oxidation of fatty acids?

Answer 8

complex 3 (CoQ) and complex 1

Question 9

what is the name of complex 1?

Answer 9

NADH ubiquinone oxidoreductase

Question 10

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 …..

Answer 10

1 - 2
2 - FMN
3 - Fe-S
4 - ubiquinone
5 - chlorine

Question 11

in complex 1 how many H+ is there a net transfer of from matrix to IMS?

Answer 11

4

Question 12

what is the name of complex 2?

Answer 12

succinate ubiquinone oxidoreductase or succinate dehydrogenase

Question 13

in complex 2 what is the function of each subunit (SDHA,B,C,D)

Answer 13

SDHA = flavoprotein
B = Fe-S protein
C = cytochrome b560
D = cytochrome b

Question 14

which 2 subunits of complex 2 are hydrophillic and in the matrix?

Answer 14

A, B

Question 15

in complex 2, which 2 subunits are hydrophobic and integral membrane proteins?

Answer 15

C, D

Question 16

complex 2 in the ETC catalyses the oxidation of succinate to what?

Answer 16

fumarate

Question 17

in complex 2, electrons from FADH2 are transferred to ubiquinone via the Fe-S clusters in which subunit, reducing it to ubiquinol?

Answer 17

SDHB

Question 18

what is the name of complex 3?

Answer 18

ubiquinol cytochrome c oxidoreductase

Question 19

each monomer of complex 3 is made of how many polypeptide subunits?

Answer 19

11 each monomer

Question 20

name the 4 active redox prosthetic groups in complex 3

Answer 20

2x b-type cytochromes (bL and bH)
cytochrome c1
rieske protein (Fe-S cluster)

Question 21

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

Answer 21

ubiquinone, 2+, semiquinone

Question 22

what is the name of complex 4?

Answer 22

cytochrome c oxidase

Question 23

in complex 4, subunits 1-3 are …… encoded and subunits 4-13 are…… encoded

Answer 23

mtDNA, nuclear

Question 24

complex 4 contains how many each of non-covalently bonded haem a and copper centres? what are they used for?

Answer 24

2 of each, for electron transfer

Question 25

which haem a and which copper centre in complex 4 form a binuclear centre, binding to oxygen to reduce it?

Answer 25

CuB and cytochrome a3 (haem)

Question 26

which complex in the ETC is the terminal electron acceptor, reducing oxygen to water and its reaction results in proton pumping?

Answer 26

complex 4

Question 27

name the 2 domains of complex 5 (ATP synthase)

Answer 27

F0 and F1

Question 28

which domain of complex 5/ATP synthase contain a proton channel?

Answer 28

F0

Question 29

which domain of complex 5/ATP synthase contains C ring subunits?

Answer 29

F0

Question 30

which domain of complex 5/ATP synthase contains additional subunits ATP6, ATP8, DAPIT?

Answer 30

F0

Question 31

which domain of complex 5/ATP synthase contains 3alpha and 3beta subunits?

Answer 31

F1

Question 32

which domain of complex 5/ATP synthase contains one gamma, one delta and one epsilon subunit, making up the central stalk?

Answer 32

F1

Question 33

which domain of complex 5/ATP synthase contains subunits b, d, F6 and OSCP which make up the peripheral stalk?

Answer 33

F1

Question 34

which domain of complex 5/ATP synthase contains an active site for ATP synthesis?

Answer 34

F1

Question 35

which domain of complex 5/ATP synthase protrudes into the matrix and which domain is embedded in the inner membrane?

Answer 35

F1 protrudes F0 embedded

Question 36

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?

Answer 36

C ring, results in conformational changes of the 3 beta subunits

Question 37

true or false, OXPHOS is under dual genetic control?

Answer 37

true

Question 38

name the 2 stands of mtDNA saying whether they are guanine rich or cytosine rich?

Answer 38

H strand is guanine rich L strand is cytosine rich

Question 39

approximately how many bp is human mtDNA? what % of the human genome does it account for roughly?

Answer 39

16,569bp, about 0.0006%

Question 40

the non coding area of the mtDNA is known as what? which 2 functions occur in this region?

Answer 40

D loop, replication initiation and transcription initiation

Question 41

what are the 4 genetic rules of mtDNA?

Answer 41

polyploid genome heteroplasmy threshold effect maternal inheritance

Question 42

why is the polyploid genome of mtDNA? what does it allow?

Answer 42

allows heteroplasmy and mtDNA inheritance

Question 43

what is heteroplasmy of the mtDNA?

Answer 43

means the mtDNA genome has two or more variants = normal and mutated DNA copies

Question 44

the threshold effect in mtDNA is when the number of ...... mtDNA copies passes a threshold, meaning the ETC and ...... fail

Answer 44

mutated, ATP synthesis

Question 45

which 2 molecules detect cells with deleterious mtDNA mutations? what colour does each turn when this activity is detected?

Answer 45

cytochrome c oxidase (brown) and SDH (blue)

Question 46

primary mtDNA disease is characterised by defective what?

Answer 46

OXPHOS

Question 47

when can primary mtDNA disease present? is there a cure? is there a wide spectrum of clinical phenotypes?

Answer 47

can present at birth, childhood or adulthood. no cure. yes