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πšπšŽπš—πš˜πš–πš’πšŒπšœ > Mitochondrial genome > Flashcards

Mitochondrial genome Flashcards

1
Q

What are the 4 functions of mitochondria?

A

β†’ Produce ATP
β†’ Haem synthesis
β†’ Neurotransmitter synthesis
β†’ Nucleotide synthesis

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2
Q

What does mitochondrial DNA look like?

A

β†’ Double stranded circular molecule

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3
Q

What does mitochondrial DNA consist of?

A

β†’ Heavy and light strand

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4
Q

How many genes does a mitochondria have?

A

β†’ 37

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5
Q

What are the mitochondrial genes for?

A

β†’ 13 oxidative phosphorylation protein subunits
β†’ 22 tRNAs
β†’ 2 ribosomal RNAs

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6
Q

Does a mitochondria have introns?

A

β†’ no

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7
Q

What is a D loop?

A

β†’ A non coding region where replication and transcription are initiated

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8
Q

How are mitochondria inherited?

A

β†’ Maternally with no recombination

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9
Q

Which of the OXPHOS proteins is not coded for by mitochondria?

A

β†’ succinate dehydrogenase

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10
Q

How is mtDNA packaged?

A

β†’ Nucleoids

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11
Q

How are nucleoids arranged?

A

β†’ one or two copies of mtDNA per nucleoid

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12
Q

What acts as a histone protein in mitochondria?

A

β†’ TFAM (transcription factor A)

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13
Q

Where does mtDNA replication start?

A

β†’ Origin of heavy strand (Oh)

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14
Q

Where does mtDNA transcription start?

A

β†’ Heavy strand promoter and light strand promoter

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15
Q

What are the exceptions to the universal genetic code in mitochondria?

A

β†’ AUA and AUG code for methionine (isoleucine in nuclear DNA)
β†’ UGA codes for tryptophan (stop codon in nuclear DNA)
β†’AGA and AGG are stop codons ( arginine in nuclear DNA)

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16
Q

What are the haplogroups of mtDNA?

A

β†’ M
β†’ N
β†’ H
β†’ L0-L3

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17
Q

What is the most common haplogroup in europe?

A

β†’ H

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18
Q

Why can mtDNA subdivide humans into discrete haplogroups?

A

β†’ It does not recombine

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19
Q

Describe the origin of mitochondria

A

β†’ a primitive eukaryotic cell ingested bacteria
β†’ the bacteria helped the cell become more complex
β†’ all bacterial DNA transferred to nucleus
β†’ remnant of DNA is mtDNA

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20
Q

Where do the proteins for replication, transcription and translation come from?

A

β†’ they are encoded by nuclear genes and imported into the mitochondria

21
Q

What are the 4 requirements for replicating mtDNA?

A

β†’ polymerase gamma (POLG) - mtDNA polymerase
β†’ TWINKLE - mtDNA helicase - unwinds DNA
β†’ Single stranded binding protein (SSBP) - keeps DNA unwound
β†’ TFAM - packages and protects mtDNA

22
Q

What is the composition of polymerase gamma?

A

β†’ heterotrimer
β†’one catalytic subunit (POLyA)
β†’ two accessory subunits (POLyB)

23
Q

What does POLyA contain?

A

β†’ 3’ to 5’ exonucleases domain to proofread newly synthesized DNA

24
Q

What is the function of POLyB?

A

β†’ enhances interactions with DNA template and increases activity and processivity of POLyA

25
Q

What type of structure is TWINKLE?

A

β†’ hexamer

26
Q

What is the function of TWINKLE?

A

β†’ Unwinds double stranded mtDNA to allow replication by POLy

27
Q

What are the 4 functions of mtSSBP?

A

β†’ Binds to SSDNA
β†’ protects against nucleases
β†’ prevents secondary structure formation
β†’ enhances mtDNA synthesis by stimulating TWINKLE helicase

28
Q

What is the main model of mtDNA replication?

A

β†’ Strand displacement model

29
Q

What kind of model is the displacement model?

A

β†’ asynchronous

β†’ two models are not replicated at the same time

30
Q

Describe the strand displacement model?

A

1) heavy strand is displaced and coated with mtSSP
2) TWINKLE helicase unwinds mtDNA
3) mtRNA polymerase synthesizes RNA primer using the light strand as a template
4) POLY uses the RNA primer to replicate DNA at OH
5) heavy strand replication passes Ol
6) stem loop structure is formed on the heavy strand preventing mtSSBP binding
7) this allows POLRMT to bind using the heavy strand as a template
8) POLy uses RNA primer to replicate the light strand DNA at Ol

31
Q

What is used to separate the two strands?

A

β†’ TOP3A

32
Q

Why are mtDNA strands named heavy and light?

A

β†’ It is richer in guanine bases

33
Q

What types of cells might have higher copies of mtDNA?

A

β†’ Cells that need a lot of energy

34
Q

When is a disease defined as rare?

A

β†’ When it affects less than 1:2000 individuals

35
Q

What do mitochondrial diseases affect?

A

β†’ highly metabolic organs that are abundant in mitochondria

36
Q

What is pearson syndrome?

A

β†’ Pancreatic dysfunction

37
Q

What is the most common mitochondrial disease presentation?

A

β†’ leigh syndrome

38
Q

What is LHON?

A

β†’ Lebers hereditary optic neuroretinopathy

39
Q

What is KSS?

A

β†’ Kearns Sayre Syndrome

40
Q

What is MELAS?

A

β†’ mitochondrial encephalomyopathy lactic acidosis stroke like episodes

41
Q

What is MERFF?

A

β†’ Myoclonus epilepsy red ragged fibres

42
Q

What is NARP?

A

β†’ Neurogenic muscle weakness ataxia retinitis pigmentosa

43
Q

How does mitochondrial disease manifest?

A

β†’ through the maternal line

44
Q

What is homoplasmy?

A

β†’ One variant of mtDNA

45
Q

What is heteroplasmy?

A

β†’ Two variants of mtDNA

46
Q

What is the amount of mutation required for disease manifestation?

A

β†’ >80%

47
Q

How are three parent embryos formed?

A

β†’ Healthy nuclear DNA is removed from patients egg cell (1)
β†’ (2) patients nuclear DNA is transplanted into donor egg with healthy mitochondrial DNA
β†’ reconstructed egg is fertilised and implanted into patient

48
Q

What kind of mitochondrial mutations are there?

A

β†’ TWINKLE or POLy can be mutated

πšπšŽπš—πš˜πš–πš’πšŒπšœ (19 decks)

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