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Genomics > The mitochondrial genome > Flashcards

The mitochondrial genome Flashcards

1
Q

How is ATP generated in the mitochondria?

A

Generation of ATP by oxidative phosphorylation

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2
Q

What are mitochondrial functions?

A
  • Haem synthesis
  • Neurotransmitter synthesis
  • Nucleotide synthesis
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3
Q

What is the structure of the mitochondrial genome?

A

Double stranded circular molecule

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4
Q

What does the mitochondrial genome consist of and not have?

A

Consists of heavy and light strands and has no introns

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5
Q

How many genes does the mitochondrial genome have?

A

Has 37 genes

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6
Q

What are the genes present in the mitochondrial genome and the amount present?

A
  • 13 Oxidative phosphorylation protein subunits
  • 22 tRNAs
  • 2 rRNAs
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7
Q

What is the D loop in the mitochondrial genome?

A

The D loop is a non-coding region where replication and transcription are initiated

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8
Q

How is the mitochondrial genome inherited?

A

Maternally inherited, no recombination

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9
Q

What does the mitochondrial genome encode?

A

Encodes proteins of oxidative phosphorylation

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10
Q

What does the non-coding region contain?

A

Contains regulatory sequences for replication and transcription

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11
Q

Where does mtDNA replication start?

A

mtDNA replication starts in the origin of heavy strand (OH)

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12
Q

Where does transcription of mtDNA start?

A

Transcription starts at the heavy strand promoter(HSP) and the light strand promoter(LSP)

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13
Q

What is mtDNA packaged into?

A

Packaged into nucleotides

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14
Q

How many copies of mtDNA are there per nucleotide?

A

One or two copies of mtDNA per nucleoid

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15
Q

What does transcription factor A(TFAM) act as when mtDNA is packaged?

A

Acts as a histone protein

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16
Q

Genetic code in vertebrate mitochondria DNA vs nuclear DNA

A
  • AUA and AUG code for methionine in mitochondria; whereas in nuclear DNA, AUA codes for isoleucine
  • UGA codes for tryptophan in mitochondria; whereas in nuclear DNA, it’s a stop codon
  • AGA and AGG are stop codons in mitochondria; whereas in nuclear DNA, it’s arginine
17
Q

What is the endosymbiotic theory of the origin of the mitochondria?

A

-Mitochondria and chloroplasts originated as bacterial cells that came to live inside larger cells

18
Q

What does the mitochondria require both of?

A

Requires both nuclear and mtDNA encoded proteins

19
Q

How many proteins does oxidative phosphorylation require?

A

Oxidative phosphorylation requires >100 proteins but mtDNA only encodes 13 of those proteins

20
Q

What must happen in order to make the 13 proteins for oxidative phosphorylation?

A

In order to make the 13 proteins for oxidative phosphorylation, protein mtDNA must be:

  • Replicated
  • Transcribed
  • Translated
21
Q

What are all the proteins involved in replication, transcription and translation of mtDNA encoded by?

A

All proteins involved in replication, transcription and translation of mtDNA are encoded by nuclear genes and imported into mitochondria

22
Q

What are all the other proteins involved in oxidative phosphorylation made by?

A

All other proteins involved in oxidative phosphorylation are made by nuclear genes

23
Q

What is the structure of the mtDNA polymerase(polymerase gamma)?

A
  • Heterotrimer protein
    • One catalytic subunit (POLA)
    • Two accessory subunits (POLB)
24
Q

What does POLgammaA contain?

A

Contains 3’-5’ exonuclease domain to proofread newly synthesized DNA

25
Q

What does POLgammaB enhance?

A

Enhances interactions with DNA template and increases activity and processability of POLgammaA

26
Q

What is the structure of mtDNA helicase(TWINKLE)?

A

TWINKLE:

-Six TWINKLE subunits

27
Q

What does mtDNA helicase, TWINKLE, do?

A

It unwinds double stranded mtDNA template to allow replication by POLgamma

28
Q

What does the mitochondrial single stranded binding protein bind to and what does it do?

A

Binds to single stranded DNA

  • Protects against nucleases
  • Prevents secondary structure formation
  • Enhances mtDNA synthesis by stimulating TWINKLE helicase activity
29
Q

Steps involved in the replication of mtDNA

A
  • Replication of heavy strand
  • Replication of light strand
  • Replication of both strands complete and segregation of daughter molecules occurs
30
Q

Replication of heavy strand

A
  • Parental heavy strand displaced and coated with mtSSBP
  • TWINKLE helicase unwinds mtDNA
  • Mitochondrial polymerase (POLRMT) synthesizes RNA primer using light strand as template
  • POLgamma uses RNA primer to replicate DNA at OH
31
Q

Replication of light strand

A
  • Heavy strand replication passes OL
  • Stem loop structure is formed preventing mtSSBP binding
  • Mitochondrial polymerase (POLRMT) synthesizes RNA primer using heavy strand as a template
  • POLgamma uses RNA primer to replicate light strand DNA at OL
32
Q

Completion of both strands

A
  • Synthesis proceeds until both strands are fully replicated

- After replication, daughter molecules are segregated

33
Q

Heavy strands

A

Heavy strands have a high composition of A and G (heavy bases)

34
Q

Light strands

A

Light strands have a high composition of C and T(light bases)

35
Q

Mitochondrial diseases

A
  • Rare monogenic diseases
  • Affect highly metabolic organs
  • Can affect one or several organ systems
  • Genetically heterogeneous
36
Q

What causes mitochondrial disease?

A

Mutation in >300 nuclear genes cause mitochondrial disease, not just mtDNA

37
Q

What determines mitochondrial disease manifestation?

A

Heteroplasmy levels determine mitochondrial disease manifestation

38
Q

How is mtDNA inherited and mutation load?

A

mtDNA is maternally inherited and inheritance of mutation load is random

39
Q

What way can be used to identify mtDNA mutations

A

mtDNA mutations can be identified by next generation sequencing

Genomics (19 decks)

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