Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

LSM3235 - Epigenetics > Topic04/05 - Mitochondrial Epigenetics > Flashcards

Topic04/05 - Mitochondrial Epigenetics Flashcards

1
Q

Briefly discuss the permeability of the mitochondrial inner and outer membrane

A

The outer membrane is permeable to small ions, while the inner membrane is impermeable.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

State the role of complex II

A

Complex II is also known as succinate dehydrogenase. Complex II converts succinate to fumarate and donates an electron to the ETC.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Which complex of the ETC does not undergo proton pumping?

A

Complex II

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

State the products of mtDNA expression

A
  1. ribosomal RNAs
  2. transfer RNAs
  3. subunits of the respiratory chain
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Components of the respiratory chain are primarily encoded for by mtDNA. TRUE or FALSE?

A

FALSE. There are more nuclear DNA encoded subunits than mtDNA encoded subunits.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Mitochondrial DNA has no CpG islands. TRUE or FALSE?

A

TRUE

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Mitochondrial DNA do not have introns. TRUE or FALSE?

A

TRUE

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

State the two possible forms of mtDNA methylation

A
  1. 5-hydroxymethyl cytosine (5hmC)

2. 5-methyl cytosine (5mC)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

State the only active DNA methyltransferase in mitochondria

A

mtDNMT1

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

State the putative role of mtDNMT1

A

Initiation and maintenance of cytosine methylation in mitochondria.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Where does mtDNA methylation occur?

A

Generally, methylation occurs in the D-loop at CpG, CpA, CpC, and CpT dinucleotides.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

tRNAs and rRNAs are also methylated in mammalian mitochondria. TRUE or FALSE?

A

TRUE. However, tRNA and rRNA methylation occurs post-transcriptionally.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Where is SAM produced?

A

Within the mitochondria.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Briefly describe the role of SAM

A

SAM (S-adenosyl methionine) is a co-substrate involved in methyl transferase activity and is capable of nuclear DNA methylation.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Mitochondria do not have histones. TRUE or FALSE?

A

TRUE.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Briefly explain the role of TFAM

A

TFAM (Transcription factor A, Mitochondria) plays a central role in the organisation of the mitochondrial genome. TFAM is important for mitochondrial transcription initiation.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

State the post translational modifications that can occur on TFAMs

A

Phosphorylation, ubiquitination, and acetylation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Describe the organisation of mtDNA

A

mtDNA is organised as nucleoids tethering the IMM

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Which post translational modification impairs TFAM binding activity?

A

Phosphorylation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Suggest the effect of D loop methylation.

A

mtDNA copy number may be impact by D-loop methylation.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What is the D loop in mtDNA?

A

The D loop acts a promoter for both the heavy and light chains of mtDNA.

22
Q

State the strand of mtDNA that codes for the majority of non-coding RNAs

A

Light strand (L-strand)

23
Q

mt ncRNA cannot escape the mitochondria. TRUE or FALSE?

A

FALSE. In fact, mt ncRNA can regulate nuclear mRNA expression.

24
Q

State the microRNA involved in Parkinson’s disease

A

miR-34b/c; it’s downregulation leads to mitochondrial dysfunction and the accumulation of fragmented mitochondria.

25
Q

State the role of miR-499, miR-140, and miR-761

A

Regulation of mitochondria fusion/fission

26
Q

Briefly describe how miR-338 regulates OXPHOS and ATP levels

A

miR-338 loaded onto RISC binds COX4 mRNA, leading to its degradation. This results in a decrease in both OXPHOS and ATP levels.

27
Q

Briefly describe how miR-210 regulates OXPHOS and ATP levels

A

Hypoxia induces the expression of HIF1-alpha, which then induces the expression of miR-210. miR-210 loaded onto RISC leads to COX10/ISCU mRNA degradation.
OXPHOS decreases, resulting in countermeasures such as membrane repolarisation and autophagy of damaged mitochondria – which in turn cause an increase in ATP levels.

28
Q

Briefly state the role of miR-378

A

miR-378 loaded onto RISC leads to caspase-3 mRNA degradation, resulting in decreased apoptosis and increased survival.

29
Q

Briefly state the role of miR-1

A

miR-1 localises to the mitochondrion and increases translation of mitochondrial-encoded transcripts. This leads to an increase in OXPHOS and ATP levels.

30
Q

Give 5 examples of miRNAs responsible for regulating mitochondrial function

A
  1. miR-34b/c
  2. miR-499
  3. miR-338
  4. miR-210
  5. miR-1
  6. miR-378
31
Q

Give an example of lncRNA responsible for regulating mitochondrial function.

A

SAMMSON

32
Q

Describe the events that occur with the lack of SAMMSON lncRNA

A

The lack of SAMMSON results in the decrease in membrane potential, resulting in mitochondrial precursor overexpression stress (mPOS) – characterised by the cytosolic accumulation of mitochondrial precursor proteins. This leads to apoptosis.

33
Q

State the protein that SAMMSON interacts with

A

p32

34
Q

State the role of linc-p21

A

linc-p21 binding inhibits VHL. VHL is an inhibitor of HIF1-alpha. This allows for more HIF1-alpha to be expressed, resulting in increased glycolysis.

35
Q

Discuss the epigenetic changes of the mitochondria in obese and insulin resistant individuals.

A

Obese and insulin resistant individuals have hypermethylated D-loop regions of mtDNA and an associated reduction in mtDNA copy number.

36
Q

Discuss the epigenetic changes of the mitochondria in non-alcoholic steatohepatitis (NASH) patients

A

Mitochondrial NADH dehydrogenase 6 (MT-ND6) is highly methylated in NASH patients.
MT-ND6 is a key component of complex I and is critical for its assembly.

37
Q

Discuss the epigenetic changes of the mitochondria in Down Syndrome cells

A

Down Syndrome cells show decreased S-adenosylmethionine (SAM) availability, resulting in hypomethylation of mtDNA.

38
Q

Discuss the role of SAM in Down Syndrome

A

Down Syndrome cells exhibit lowered SAM levels, resulting in the hypomethylation of mtDNA.
Furthermore, the lowered SAM levels results in decreased GSH levels, which are required to counter oxidative damage. (GSH –> GSSG)

39
Q

Suggest why mtDNA is susceptible to ROS damage

A

mtDNA is localised near the IMM, which is also the site of ROS production due to OXPHOS.

40
Q

Discuss the epigenetic changes of the mitochondria in early-stage Alzheimer’s Disease

A

Increased D-loop methylation and reduction of methylation in MT-ND1

41
Q

Discuss the epigenetic changes of the mitochondria in Parkinson’s

A

Decreased D-loop methylation and maintenance of MT-ND6 methylation within the substantia nigra

42
Q

Compare and contrast epigenetic changes of the mitochondria in Alzheimer’s and Parkinson’s

A
  1. Alzheimer’s: increased D loop methylation; Parkinson’s: decreased D loop methylation
  2. Alzheimer’s: decreased MT-ND1 methylation; Parkinson’s: maintained MT-ND6 methylation
  3. Alzheimer’s and Parkinson’s: unchanged levels of 5hmC in D-loop, MT-ND1, and MT-ND6.
  4. Alzheimer’s and Parkinson’s: presence of 5mC in CpG and non-CpG sites in the human brain
43
Q

Discuss the epigenetic changes of the mitochondria in cancer (colorectal)

A

Increased demethylation of D-loop.
The increase in D-loop demethylation is associated with a higher copy number, which may result in the increase of ND2 expression (complex I subunit)
The increased mtDNA copy number also contributes to increased cell proliferation and apoptosis resistance.

44
Q

What is 5-AZA?

A

5-AZA is a DNA hypomethylating agent

45
Q

State the possible effects of elevated mtDNA copy number in cancer cells.

A
  1. Increased cell proliferation
  2. Reduced apoptosis
  3. Relative retardation of G0/G1 phase
46
Q

Discuss the epigenetic changes of the mitochondria in CVD (cardiovascular diseases)

A

Increased platelet mtDNA methylation

47
Q

State the role of SOD2

A

SOD2 is produced in the nucleus and migrates to the mitochondria. SOD2 produces H2O2 from O2-. (superoxide). H2O2 deactivates HIF-1α.

48
Q

Discuss the epigenetic changes in the mitochondria in pulmonary hypertension

A

Overexpression of DNMT1 and DNMT3B leads to hypermethylation of CpG islands in the promoter of SOD2 gene.
This results in an impaired H2O2 mediated signaling, activates HIF-1α, creating a proliferative, apoptosis resistant state.

49
Q

Discuss the epigenetic changes in the mitochondria (or epigenetic changes relating to the function of the mitochondria) in aging

A
  1. Increased MT-RNR1 methylation. MT-RNR1 encodes for 12S rRNA in the mitochondria, and high methylation levels exhibit a higher mortality risk (only observed in women)
  2. Increased DNA methylation of COX7A1 (in the nucleus). COX7A1 is a respiratory chain component, hence its increased promoter methylation results in decreased oxidative capacity of the mitochondria.
50
Q

Discuss the epigenetic changes induced by mitochondrial stress

A

Mitochondrial stress induces UPR^mt (unfolded protein response). This causes chromatin reorganisation and compaction of the nucleus – leading to longevity of the cell.

LSM3235 - Epigenetics (7 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions