Brainscape's Knowledge GenomeTM


Top Flashcards (Certified)
All Flashcards

Genetics of cell growth and division > Jones 5-8 > Flashcards

Jones 5-8 Flashcards

1
Q

Mitochondrial morphology

A

Size and shape of mitochondria varies between cell types and with cell cycle stage
Double membrane
Folds of cristae – large surface area
Enlarged mitochondria are often associated with disease state

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

How do mitochondia exist?

A

as constantly-evolving networks within the cell cytoplasm rather than totally separate organelles
Continuous fusion and division

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

How are mitochondria dynamic organelles?

A

Balance of fusion and fission

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

Why are mitochondrial dynamics important?

A
  • Mitochondria can’t be made; they have to be inherited in cell divisions
  • Accommodating cell growth
  • ATP generation in oxygen poor regions of the cell e.g. move mitochondria to different areas of the cell
  • Redistribution of mitochondria with cell division
  • Genetic complementation – defects in one mitochondria are compensated for by others
  • Important for cell survival
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What are the three central players of mitochondrial dynamics?

A

1) Mitofusins
2) OPA1 (M) /Mgm1 (Y)
3) Drp1 (M) /Dnm1 (Y)
GTP-hydrolyzing proteins (GTPases) that belong to the dynamin superfamily

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

What is the function of mitofusins?

A

MOM fusion

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

What is the function of OPA1/Mgm1?

A

MIM fusion

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

What is the function of Drp1/Dnm1?

A

division of outer and inner mitochondrial membranes

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

What is used in yeast to study mitochondria?

A

MitoTracker Red: Selectively localises to mitochondria; covalently attaches to membrane proteins
Mito-GFP: Expressed in only one parental strain; under control of Gal1/10 promoter

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

After cell fusion what happens to the two mitochondrial populations?

A

Almost complete fusion

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

What happens in Drosophila melanogaster sperm development?

A

Mitochondria undergo dramatic reorganisation – essential for fertility
Failure in mitochondrial fusion - infertility
fzo gene identified: encodes the founding member of the conserved mitofusin GTPase family
fzo required for mitofusion and fertilisation

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

What was conclded from the ts fzo mutants

A

mitochondrial fusion cannot occur without functional mitofusion
In mutants you get unopposed fission so get individual mitochondria and no networks

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

What happens if mitochondrial fusion is impaired in mammals?

A

Knockout mice lacking Mfn1 and/or Mfn2 (mammalian mitofusins) die due to placental defects; cells have fragmented mitochondria
Human neurodegenerative disorder Charcot-MarieTooth disease type 2A results from mutations in human mitofusin Mfn2

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

What does a mutation in mgm1 cause?

A

a decrease in fusion events on the MIM

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

What are the main steps of mitochondrial fusion?

A

1) Docking/tethering: Mitofusin dimers form
2) GTP hydrolysis: Outer membranes fuse
3) Tethering and fusion: Inner membranes fuse via Mgm1 (yeast), opa1 (mammalian)

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

What is another potential function of opa1?

A

maintenance of cristae structure

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

Why is mitochondrial fission important?

A

• Important for the remodelling and rearrangement of mitochondrial networks, as well as for enabling mitochondrial segregation during cell division

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

What is the phenotype of a dnm1 knockout?

A

large nets of mitochondria due to failed mitochondrial division

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

How do dnm1/drp1 proteins function?

A

Dnm1 (yeast)/Drp1 (mammals) protein physically associates with other copies of itself in curved structures on outer surface of mitochondria.
Curved Drp1/Dnm1 structures constrict and pinch off mitochondria using the energy from GTP hydrolysis

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

What are the main steps of mitochondrial fission?

A

1) Drp1 recruitment: Fis1 recruits Drp1 to membrane
2) Oligomerization: Multiple Drp1 molecules join together to form scission machine
3) Fission: GTP hydrolysis fuels membrane scission

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

How is fusion/fission regulated?

A

Balanced by mitofusin levels

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

How does regulation occur at many levels/ cellular contexts?

A
  • Protein stability
  • Protein cleavage
  • Protein conformation
  • Changes such as phosphorylation
  • Protein localization via association with binding partners
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

How do mitochondrial fission proteins function?

A

Phosphorylation
Ubiquitination
E.g. Drp1 activity controlled by phosphorylation at different sites
Through action of PKC/Cyclin B/PKA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

How do mitochondrial fusion proteins function?

A

Proteolysis
Ubiquitination
E.g. ubiquitin-mediated degradation of Fzo1
E.g. proteolytic cleavage of inner membrane dynamins (Opa1/Mgm1)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
What is mitophagy?
Mitochondrial autophagy
26
What is the purpose of mitophagy?
Important for maintenance of healthy mitochondrial population Response to changes in mitochondrial membrane potential
27
How does mitophagy remove defective mitochondria?
1) damaged/defective mitochondria tagged with a specific kinase and ubiquitin ligase 2) mitochondrial fusion disabled 3) destruction by proteosome
28
How is mtDNA organised?
Into nucleoids | nucleoids distributed throughout mitochondrial network
29
What are nucleoids?
MtDNA packaged with proteins | 1-10 mtDNA copies per nucleoid and 10-1000 nucleoids per cell
30
What happens to nucleoids with decreased fission?
nucleoids cluster together and lose even distribution throughout network
31
Where are nucleoids during fission?
nucleoids present at 80% of fission sites 63% of the time at both tips 37% of the time at one only
32
Do nucleoids move to the fission sites or does the location of the nucleoids dictate where division occurs?
not clear
33
What is the ERMES complex and what does it do?
ER-mitochondria encounter structure | complex associates with mitochondria fission sites. Present at 60% of division sites
34
Why is mitochondrial fusion/fission important for mtDNA integrity?
* MtDNA undergoes frequent mutations due to close proximity with the ROS generation site * Mitochondrial dynamics plays an important role in compensating for these mutations * Mammalian cells with defects in mitochondrial fusion or fission machinery have reduced mtDNA content and an increased rate of mtDNA mutation
35
What is the Evidence for complementation?
Studied restoration of OXPHOS function through complementation in cybrids - Cybrids are cytoplasmic hybrids OXPHOS capacity was measured in mammalian cells • Mutants had a much lower level • Cybrids gave an intermediate level Deletion/repair of mutant mtDNAs? Segregation of mutated mtDNAs and elimination by mitophagy?
36
How does mitochondrial morphology change at G1/S phase transition?
* needs increase in ATP levels to generate biomolecules | * To increase the efficiency of ATP synthesis, mitochondria fuse and elongate.
37
How does mitochondrial morphology change during mitosis?
Mitochondrial fragmentation is needed to ensure distribution of mitochondria to daughter cells.
38
What is essential for mitosis-related mitochondrial fission ?
Drp1
39
How is Drp1 phosphorylated?
by the cdk1/cyclinB MPF complex at S585A
40
How is mitochondria distributed during asymmetric cell division?
* Mitochondria either move in a retrograde or anterograde fashion – move to either end * Proposed that fitter mitochondria are more motile and are moved to the bud cell tip – have to move further – get healthier mitochondria in bud cell * Sticking points. Site-specific anchorage retains mitochondria to certain locations. * Quality control. Which mitochondria end up in the bud? Mitochondria anchored in bud tip have fewer ROS
41
What are the quality control mechanisms?
* Mitochondrial fusion repairs low-functioning mitochondria by intra-organellar complementation * Molecular chaperones bind to and stabilize unfolded proteins * Proteases both within and outside the organelle degrade damaged mitochondrial proteins * Mitophagy and mitochondrial fusion and fission eliminate mitochondria that are beyond repair
42
What are the mitophagy proteins?
PINK1 | PARKIN
43
What is PINK1?
PTEN-induced putative kinase protein 1 (serine threonine kinase)
44
What is PARKIN?
E3 ubiquitin ligase
45
How do PINK and PARKIN function in healthy mitochondria?
Functional membrane potential | PINK1 is imported and degraded
46
How do PINK and PARKIN function in defective mitochondria?
* Lack of membrane potential * PINK remains on surface and recruits PARKIN * Mitochondrial proteins ubiquitinated * Destruction by mitophagy
47
What degenerates in Parkinson’s disease?
degeneration of the dopaminergic neurons in substantia niagra leads to reduced Complex 1 activity in the substantia niagra
48
What mutations have been linked to familial PD?
Pink1, Parkin and mtDNA (amongst others)
49
Why do you seen mitochondrial dysfunction in PD?
result of defective mitophagy
50
Yang et al., 2008 | Parkinsons disease
Organism: drosophila and human cell lines PINK1 plays a role in regulating dopaminergic physiology PINK1 -> fis1 -> Drp Pink1 in a positive regulator of mitochondrial fission
51
How is Autosomal Dominant Optic Atrophy caused?
Affects mitochondrial encoded complex 1 subunits Mutation in Opa1 (optic atrophy 1) Associated with mtDNA depletion
52
What are the symptoms of DOA?
o Opthalmoplegia o Ataxia o Deafness o Resulting from decreased OXPHOS
53
Ban et al., 2010 | DOA
Organism: Mice and cell lines OPA1 is essential for MIM fusion OPA1 interaction with membrane: stimulates higher order assembly enhance GTP hydrolysis cause membrane deformation into tubules mutant OPA1 -> fragmented mitochondria -> fusion is prevented
54
How is Charcot Marie tooth type 2A (CMT2A) caused?
* Most common hereditary peripheral neuropathy * Most of the CMT2A cases involve Mfn2 mutations, mainly in the GTPase domain. Can be gain of function or loss of function * Defects in mitochondrial motility have also been linked to CMT2A * CMT2A patients have reduced OXPHOS which has been linked with increase in mtDNA deletion
55
Chapman et al., 2013 | CMT2A
Organism: zebrafish MFN mutation causes fusion failure leads to motor dysfunction phenotype adult onset and progressive motor defects altered motility associated with NMJ defects
56
Huntingtons diease | Shirendeb et al., 2011
``` Brain tissue samples abnormal dynamics in HD high levels of fission proteins low levels of fusion proteins CypD upregulated and increases with HD progression increased expression of mtDNA encoded complexes in ETC lower mitochondria function more oxidative damage ```
57
Mutations in Htt cause?
``` Mitochondrial imbalance impairred axonal transport decreased mitochondria function damages neurons colocalises with drp at MOM ```
58
Neurodegenerative disease | seo et al., 2010
Neurons have a high metabolic demand Alzhiemers - AB accumulation causes mitochondria dysfunction and aberant structures AB induces fission
59
Ageing | Seo et al., 2010
``` direct link between mtDNA mutations and ageing decline in Mt turnover reduced mitochondrial bigenesis inefficient mitochondrial degradation protective mechanisms are impaired organelle plasticity decreases lysosomal autophagy decreases ```
60
How is degradation of a single mitochodria different to that of a mitochodrial network?
individual defective mitochondrial proteins are degraded by the proteasome sections of mitochondria are removed by mitophagy

Genetics of cell growth and division (4 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions