Brainscape's Knowledge GenomeTM

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


See full index

BMIS 435 > Leary > Flashcards

Leary Flashcards

1
Q

What are mitochondria

A

cellular organelle
Double membrane bound
Contain mitochondrial DNA which is maternally inherited

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

Inner vs outer mitochondrial membrane

A

Inner mitochondrial membrane is protein loaded, contains the ETC, and is impermeable which is needed for the proton gradient

Outer mitochondrial membrane is permeable with many holes, doesn’t have many proteins

These properties are relevant to how the organelle functions as a whole and contributes to cellular homeostasis

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

Where is the mtDNA, Krebs cycle, and metals

A

matrix of mitochondria

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

What are cristae? Which enzymes are concentrated there?

A

Inner folds of the mitochondrial membrane
Used to increase surface are to put more proteins and enzyme to produce more ATP

Enzymes of oxidative phosphorylation are concentrated within the cristae

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

T/F the function of the inner membrane is different depending on where it is

A

true

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

What are the reducing equivalents used in the ETC

A

NADH feeds into complex I and FADH2 feeds into complex II

These are needed for the ETC to function

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

Why might one tissue have more cristae than another

A

The inner membrane architecture is optimized for the tissue it functions in

Tissues that need more ATP will have more cristae

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

T/F mitochondria are static

A

False its a dynamic reticulum that responds to intracellular cues and extracellular stimuli

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

What are some cues that can cause the mitochondria to hyperfuse to become one organelle

A

Starvation
Translation inhibition
Viral infection
Conditions when differentiation is important

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

When would the mitochondria hyperfragment?

A

Cancer, bacteria, OXPHOS poisons
Conditions when cell division is important

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

What enzymes drive Fusion

A

MFN1 and MFN2

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

L-OPA1 vs S-OPA2

A

L-OPA1 is required for fission
S-OPA1 is required for fusion

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

Why are mitochondrial dynamics important

A

Adapting organelle function to a broad range of cues
Failure to appropriately balance fission and fusion will impair organelle function and cellular homeostasis

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

What are some basic challenges of mitochondrial content

A

They have a large proteome and require many proteins to function
They have their own genome which encodes crucial polypeptides
They have to coordinate expression of nuclear and mtDNA-encoded protein products (crucial to maintaining or expanding existing populations of organelles)

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

Describe the number of organelles and mitochondrial volume across tissues

A

Number varies between 1 and 1000
Fold difference ranges from 2-40%

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

how is the balance of mitochondria maintained

A

maintained between rates of biogenesis and degradation

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

What is mitophagy

A

Self-eating process in mitochondria, way to degrade mitochondria

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

Mitochondria alter their _____ and ____ to fulfill diverse functions

A

shape and number

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

why are fission and fusion important

A

Allows mitochondria to respond to internal and external cues and adapt to their environments ot fulfill the necessary conditions to survive

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

What are the 6 essential processes for maintaining homeostasis that the mitochondria plays a role in

A

ATP production
Epigenetics
Peroxisome biogenesis
Fe-S cluster synthesis
Apoptosis & cell cycle control
Regulation of cellular metal ion homeostasis

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

How does cytochrome C initiate apoptosis

A

Cytochrome C is tethered to the inner membrane under normal circumstances but when the inner membrane is compromised cytochrome C can be released and initiate apoptosis

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

Which processes do cytochrome c oxidase assembly affect?

A

ATP production and regulation of cellular metal ion homeostasis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

How many subunits are encoded in nuclear and mtDNA of the mitochondria

A

4 complexes responsible for making the ETC and fifth for creating ATP

only complex 2 is completely from nuclear DNA and the other complexes are a mix of mtDNA and nuclear

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

What are some basic characteristics of mtDNA

A

16.6kb double stranded, circular genome
genome was compacted because it is more efficient
Present in multiple copies per organelle
Maternally inherited
In the matrix in order to protect it
Encodes 13 proteins
Lacks introns

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Where is the mtDNA bottleneck during oogenesis

A

QC step

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Can mitochondrial diseases be heterogenic

A

no, will only be a carrier

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

T/F mitochondrial diseases are extraordinarily homeogeneic

A

false heterogeneic

28
Q

Is OXPHOS complex biogenesis different from the nucleus

A

fundamentally yes

29
Q

What is cytochrome c oxidase

A

protein in complex 4 of ETC
used as a model protein

30
Q

Cytochrome C oxidase structure

A

14 structural subunits
3 mtDNA-encoded
11 nuclear-encoded

31
Q

Why use a cytochrome C oxidase as a model protein

A

Consists of nuclear and mtDNA encoded subunits

Rate-limiting to ATP production under a range of physiological conditions

Commonly observed metabolic lesion

Most thoroughly characterized from a genetic, biochemical and molecular biological perspective

32
Q

Why are nuclear subunits important?

A

They are important for stability, affect rates of activity, and alter the structure of the enzyme

33
Q

What are 2 important prosthetic group for cytochrome c oxidase

A

COX1 and COX2

34
Q

Describe the assembly of cytochrome c oxidase

A

Assembly is highly ordered and modulated in nature
4 stages

35
Q

How do mutations in mtDNA occur

A

spontaneously or inherited

36
Q

What is the threshold effect

A

tissues accumulate mutant mtDNA and once they reach a threshold it starts to have an effect
Explains later onset of disease manifestation

37
Q

What were the barriers or challenges with respect to diagnosing the genetic basis of these diseases?

A

Lack of adequately diverse and sensitive diagnostic tools

incomplete or absent sequence coverage of relevant regions of the human genome

lack of an adequate model system to study human disease

Heterogeneity

38
Q

What is the genetic explanation for early onset disease?

A

The assembly of the cytochrome C oxidases uses a toolbox of many different factors which are essential to the assembly

Mutations to these factors could explain the early onset of the disease

39
Q

mtDNA vs nuclear DNA

A
40
Q

SCO1 vs COX

A

SCO1 is the yeast version of COX10

COX10 could rescue yeast SCO1 null cells but the yeast SCO1 could not rescue COX10

41
Q

What might be some reasons for not being able to use yeast to study a humane mitochondrial disease gene?

A

Can’t interact with the correct proteins and proteins usually work in tandem

42
Q

What was the visualization technique that revolutionized mitochondrial disease work

A

blue-native PAGE

43
Q

How were SCO1 and SCO2 first identified

A

Was identified through the yeast PET mutant collection. Mutations in functional yeasts were related to a single enzyme or biosynthetic pathways which helped characterize different defects

They were identified as high copy suppressors of a yeast COX 17 mutant

44
Q

What do mutations in human SCO result in

A

severe early onset disease with a fatal outcome

45
Q

What are the simples ways to rescue disease caused by mutations in a given gene like SCO1 or SCO2? Problems?

A

Genome editing: Ethical dilemmas
Re-introduce the wild-type protein into the system: Not feasible for short-lived protein, costly, systemic delivery

Treating with copper: Was able to rescue COX deficiency in SCO2 patient cells, can rescue heart but not brain function

46
Q

Why can copper treatment rescue SCO2 null cells but not SCO1 null cells

A

Coppers need to insert into the protein and it was shown that SCO1 acted as the insertase

47
Q

How can ubiquitously expressed mutations be heterogeneic

A

Tissue specific:
Difference in half-life
Abundance of a given COX assembly factor
abundance of metals
Unique effects on protein

48
Q

What were historic challenges in mitochondrial disease diagnosis

A

Clinical heterogeneity
Limited diagnostic toolbox (old tools)
Lack of reference genome sequence (reliance on large pedigrees)
Reliance on a single model organism (inadequate models)

49
Q

What are on-going challenges with mitochondrial disease diagnosis

A

clinical heterogeneity
Multiple model organisms available
We have the human genome sequence now, however if the mutation is in the intron that may affect splicing and we do not have intron sequences

50
Q

What is a mitochondrial disease treatment that is currently in phase 2 trials and could be a viable strategy? how does it function? Barrier?

A

Mitochondrially targeted nucleases

Promotes degradation of mutant mtDNA

The nuclease recognizes the mutation and cuts the DNA

Need to be put in via a viral delivery system which may not work for isolated organs, nuclease is very large

51
Q

Could supplementation be used to treat mitochondrial disease

A

Protein supplement is difficult due to half-life issues and SCO2 lives in a membrane
Vitamin supplementation has minimum benefit
Thin air does not work because it results in hypoxia

52
Q

What is the effect of thin air supplementation

A

Rescues the mitochondrial DNA, but hypoxia results in cancer and death

53
Q

Can copper supplementation be used to overcome genetic defects that impede copper site biogenesis

A

When copper is unbound it can produce many free radicals and cause damage

Can rescue heart defects but not brain

The copper needs something protein to cross the BBB

54
Q

What are some tissue-specific challenges associated with COX deficiency

A

Differences in half-life of the holoenzyme
Differences in abundance of a given COX assembly factor
Differences in abundance of metals essential for assembly

55
Q

How can unique allelic variants in a single COX assembly factor give rise to distinct, tissue-specific forms of disease?

A

Unique effect on the residual function of a protein
Unique effects on the residual functions of a protein

56
Q

What is cardiolipin

A

Cardiolipin is a unique protein to the inner mitochondrial membrane

Cardiolipin curves the membrane to promote cristae formation

Allows for mitophagy among other functions

57
Q

What is the rate-limiting enzyme for cardiolipin biosynthesis

A

Tafazzin
It is essential in the final step of cardiolipin biosynthesis

58
Q

What is Barth syndrome

A

Results from mutations in TAZ, the gene encoding Tafazzin

59
Q

When does the mitochondria fragment or fuse

A

Fragment to go into a resting state and remove damaged organelles
Fuse for the complementation of gene products and requires the cooperation of the entire compartment, in response to stress and starvation

60
Q

What happens when the quality control machinery cannot maintain proteostasis?

A

Protein folding will be impaired, when there is membrane potential damage, proteases cannot help resulting in no proton motor force and autophagy

61
Q

What is the quality control mechanism for mito

A

Contains many proteases in every subcompartment
Processing peptidases and ATP-dependent proteases sense folding stated and ensure quality control

62
Q

Why is autophagy important

A

Important for garbage disposal
It is important for adaptive responses as it provides nutrients and adapts to stress conditions

63
Q

Where is quality control machinery concentrated? What 2 things does it fuse together)

A

Concentrated around the phagophore
Fuses autophagosome and lysosome

64
Q

Micro & macroautophagy share a common set of essential ____ proteins

A

ATG (autophagy) proteins which are critical for induction of the process and autophagosome formation

65
Q

5 things

What are the broad stages of autophagy

A

Phagophore biogenesis
Autophagosome formation
Autophagosome maturation (fusion with lysosome)
Breakdown of cargo
Recycling

Specific types of autophagy requires unique elements

66
Q

Functions of PINK1 and PARKIN? What do mutations in these cause?

A

PINK1 recruits PARKIN to the damaged mitochondria
PARKIN poly ubiquitinates VDAC1
P62 then binds poly Ub-VDAC1
This facilitates the interaction of the organelle with core autophagic machinery

Results in parkinsons disease

67
Q

Inability to clear defective mitochondria from neuronal cells contributes to the clinical progression of _________ __________

A

Parkinsons disease
Damages neurons

BMIS 435 (17 decks)

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