Mitochondrial genome

Question 1

Mitochondrial genome

Answer 1

• Double stranded circular molecule (16.6kb) (15,000x smaller than chromosome 1)
• Consists of the heavy and light strand
• Multicopy genome (10-100,000 copies per cell)
• 37 genes
13 oxidative phosphorylation protein subunits
22 transfer RNAs

Question 2

How many ribosomes

Answer 2

2 ribosomal RNAs
• No introns
• D-loop is a non coding region where replication and transcription are initiated
• Maternally inherited, no recombination

Question 3

What does the mitochondrial genome code

Answer 3

Proteins of oxidation phosphorylation

OXPHOS consists of five enzymes complexes CI - CV

Question 4

Non-coding region (NCR) contains regulatory sequences for replication and transcription

Answer 4

mtDNA replication starts in Origin of heavy strand (OH).
Transcription starts at Heavy strand promoter (HSP) and
Light strand promoter (LSP)

Question 5

mtDNA and nucleotides

Answer 5

• mtDNA is packaged into structures called nucleoids
One or two copies of mtDNA per nucleoid
Transcription factor A (TFAM) acts as histone protein

Question 6

Exceptions to the universal genetic code

Answer 6

• Genetic code in vertebrate mitochondria
AUA and AUG code for methionine (AUA codes for isoleucine in nuclear DNA)
UGA codes for tryptophan (stop codon in nuclear DNA)
AGA and AGG are stop codons (not arginine)

Question 7

mtDNA OXPHOS proteins

Answer 7

13 proteins

Question 8

OXPHOS requires how many proteins?

Answer 8

More than 100 proteins

Question 9

How to make OXPHOS proteins

Answer 9

mtDNA needs to be
Replicated
Transcribed
Translated

Question 10

Mitochondrial DNA replication machinery

Answer 10

DNA processing and repair - DNA2, MGME1, RNASEH1
Unclear function - MPV17
dNTP pool - DGUOK, RRM2B, TK2, TYMP

Question 11

Mitochondrial DNA polymerase

Answer 11

Polymerase gamma (Polg)
Heterotrimer protein
One catalytic subunit (POLgA)
Two accessory subunits (POLgB)

Question 12

POLgA

Answer 12

Contain 3’ – 5’ exonuclease domain to proofread newly synthesized DNA

Question 13

POLgB

Answer 13

Enhances interactions with DNA template and increases activity and processivity of POLgA.

Question 14

Mitochondrial DNA helicase twinkle

Answer 14

• TWINKLE
Hexamer – six TWINKLE subunits
• Unwinds double stranded mtDNA template to allow replication by Polg

Question 15

Mitochondrial single stranded binding protein (mtSSBP)

Answer 15

• Binds to single stranded DNA
Protects against nucleases
Prevents secondary structure formation
Enhances mtDNA synthesis by stimulating TWINKLE helicase activity

Question 16

Strand displacement model of mtDNA replication

Answer 16

Replication of heavy strand begins at OH
Replication of light strand begins at OL
Replication of both strands completed
Segregation of daughter molecules

Question 17

Leigh syndrome

Answer 17

Most common mitochondrial disease presentation

Question 18

LHON

Answer 18

Leber’s Hereditary Optic Neuroretinopathy

Question 19

KSS

Answer 19

Kearns-Sayre Syndrome

Question 20

MELAS

Answer 20

Mitochondrial Encephalomyopathy Lactic Acidosis Stroke like episodes

Question 21

MERF

Answer 21

Myoclonus Epilepsy Red Ragged Fibres

Question 22

NARP

Answer 22

Neurogenic muscle weakness Ataxia Retinitis Pigmentosa