Brainscape's Knowledge GenomeTM


Top Flashcards (Certified)
All Flashcards

Molecular Cell Biology > Lecture III > Flashcards

Lecture III Flashcards

1
Q

What are the 2 classes of dynamin GTPases?

A

mitofusins (MFN1 & MFN2) for the fusion of the OMM

OPA1 for the fusion of the IMM

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

What can be observed in mitochondria if MFN1 is genetically removed?

A

the mitochondrial network becomes highly fragmented

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

What is the main player between MFN1 & MFN2?

A

MFN1

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

What are heptad repeats (HR)?

A

found in MFN1 and MFN2, and they are helical structures important in trans interactions between MFN1 proteins localized in nighboring mitochondria

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

What kind of proteins are MFN1 & MFN2?

A

transmembrane proteins

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

Describe OPA 1:

!!!

A

GTPase protein that undergoes a finely regulated process of transcriptional regulation and post-translational regulation

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

How many splicing variants of OPA1 are there for humans? for mice?

A

8

4

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

What do the OPA1 splicing variants depend on?

A

inclusion or exclusion of specific exons that determine the cleavage site doe post0translational processing

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

Where are OPA1 proteins imported?

A

into the mitochondria and inserted into the IMM

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

What do the upper bands of this western blot on HeLa cells lysate represent? lower bands?

A

long forms of OPA1 (L-OPA1)

isoforms generated upon cleavage

**this is a healthy cell

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

What mediates the fusion of mitochondria?

A

L-OPA1

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

What are OMA1 and YME1L? What do they do?

A

transmembrane proteins that protrude the intermembrane space

cleave OPA1 and give soluble short forms that accumulate in the IM space

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

In cases of stress, describe what happens with OMA1:

A

OMA1 is over-activated and it over-processes OPA1 so there are no more L-OPA1

*eventually OMA1 is degraded upon cleavage of OPA1 since its activity would result in a danger for the cell

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

How can OPA1 mediated the fusion of the IMM?

A

L-OPA1 mediates the fusion of the IMM through heterotypic cell interactions with cardiolipin (only found in IMM) of the neighboring mitochondrion

*through protein lipid interactions

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

MFN mediates the fusion of…

A

OMM

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

L-OPA1 mediates the fusion of…

A

IMM

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

S-OPA1 mediates the fusion of…

A

not defined

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

What can L-OPA1 do at the base of cristae?

A

oligomerize and generate tight junctions at the base of the cristae when combined with a lot of proteins as MICOS complex and cardiolipin

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

Why is cristae formation important?

A

necessary for oxidative phosphorylation

confinement of the cytochrome c

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

What are the 3 models that describe the organization of the respiratory chain?

A

fluid model

solid model

plasticity model

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

What is the fluid model of the respiratory chain?

A

complexes are randomly distributed and they float around the membrane

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

What is the solid model of the respiratory chain?

A

all complexes are closely packed

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

What is the plasticity model of the respiratory chain?

A

combination of the fluid model and the solid model

it is the most accepted and confirmed by the isolation of complexes with a protocol of Blue native PAGE›

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

Are respiratory chain complexes organized?

A

yes, they are organized in an optimal arrangement in order to maximize electron flux and ATP production

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
What do mutations on the proteins of that maintain cristae shape result in?
widening of the cristae structure, with a consequential loss of ATP synthesis and release of cytochrome c
26
What mediates mitochondrial fission?
Drp1
27
What do patients with a mutation in Drp1 have?
encephalopathies and motor behaviors *most die before 10 years of age
28
What is Drp1?
cytosolic protein that is recruited to OMM upon fission or physiological stimulus
29
What receptors does Drp1 bind to?
Fis1 Mff MiD49 MiD51
30
What happens after Drp1 binds to a receptor?
forms a contractile ring around the OMM after the oligomerization
31
Upon GTP hydrolysis, Drp1 mediates _______.
the separation of the OMM
32
Where are the Drp1 receptors located?
all over the OMM
33
What is mitokinesis?
division of the mitochondria mitochondria uses the cytoskeleton and actin myosin fibers to contract to divide into 2 mitochondria once the mitochondria meets with the ER, a preconstriction site is generated and there is nucleation of the actin cytoskeleton myosin 2 is recruited to fission site myosin 2 activity results in the constriction of the mitochondria and the generation of 2 daughter mitochondria dyamin (Dyn2) may be impacted
34
What could happen if the mitochondria cannot control fusion and fission events?
hyper-fragmentation of the mitochondrial network formation of giant mitochondria
35
What causes hyper-fragmentation of the mitochondrial network?
OPA1 or mitofusion mutations
36
What causes the formation of the giant mitochondria?
Drp1, which prevents the fission process *results in a huge mitochondria that accumulates ROS **very dangerous for all cells but especially neurons
37
What have the mitochondria shown in terms to adaptation?
they are able to adapt in response to the cell's nutrients
38
What happens if the cell is in a condition of ss deprivation?
mitochondrial network has the tendency to hyperfuse
39
What happens if the cell is in a condition with high levels of nutrients?
mitochondrial network has the tendency to be fragmented
40
What ahppens if the mitochondria are completely depolarized?
they are targeted to mitophagy
41
How are cells targeted for autophagy/mitophagy?
the cargo (in this case: mitochondria), is ubiquitinated which allows for the interaction with specific receptors
42
What triggers mitophagy?
hypoxia and ROS, which can alter and dissipate the mitochondrial membrane potential
43
Where is PINK1 integrated?
inner membrane
44
Hw is PINK1 delivered to the inner membrane?
through a pre-sequence, which is recognized by TOM/TIM pathway pre-sequence is then cleaved and the PINK1 is imported and localized in the inner membrane where it can phosphorylate its substrate
45
What is PINK1 involved in?
mitophagy
46
What are the 2 proteins involved in mitophagy?
PINK1 and Parkin
47
What 2 proteins are mutated in the genetic form of Parkinson's disease?
PINK1 and Parkin
48
What happens in a mitochondrial damage condition that depolarizes the membrane?
PINK1 is no longer imported → accumulation of OM → dimerization and auto-phosphorylation of PINK1 → OM proteins are ubiquitinated → proteins are retrotranslocated to the cytosol for degradation *PINK1 and the proteins of the OM phosphorylate themselves in this process **this combined post-transcriptional modification recruits Parkin, an E3ubiquitin-ligase, to the OMM
49
What does the combined post-transcriptional modification process result in?
further ubiquitination of the OM proteins the high ubiquitination and phosphorylation of the OM act as a recruitment signal for p62, which is the receptor for the autophagosome
50
What is the receptor of the autophagosome?
p62
51
Why is fission important?
leads to the biogenesis of mitochondria pre-requisite for the degradation of mitochondria
52
What was discovered last year about a fission event needed for mitochondrial biogenesis?
a mid-zone fission is needed, which is mediated by the interaction of the mitochondria and ER
53
How does a cell know when fission leads to mitophagy?
fission is located at the periphery where there is lots of rubbish like damaged and oxidized proteins
54
What is the mechanism where fission occurs at the periphery to signal for mitophagy through the interaction of the mitochondria and lysosomes mediated by?
Mitochondrial fission 1 protein (FIS1)
55
What does FIS1 bind to?
Drp1
56
Where is calcium abundant?
outside the cells
57
Why is the fine control of calcium important?
calcium is a second messenger and involved in lots of controlled pathways *loss of its control can destabilize homeostasis
58
What can anti-porters do?
extrude calcium outside the cell
59
What can ATPases (aka SERCA) do?
internalize large amounts of calcium inside the ER
60
How can mitochondria internalize calcum?
they can internalize calcium through a uniporter called Mitochondrial Calcium Uniporter (MCU) located in the IMMM
61
How does MCU work?
ligand binds to G-coupled protein receptor at the plasma membrane that leads to the release of inositol-3-phosphate (IP3), which acts as a ligand for IP3 receptor located on the ER membrane *this interaction leads to the release of calcium from the ER lumen, where it will generate a flux that moves from the ER to the mitochondria
62
How can calcium enter the mitochondria?
using VDAC proteins, which are large β-barrel proteins that are porins that are poorly selective for ions
63
How can calcium be exported outside of the mitochondria?
using antiporters like Na+/Ca2+ or proton/Ca2+
64
Why is the Ca2+ entrance inside the mitochondria peculiar?
MCU has a low affinity for calcium *this means high conc. of calcium is needed to open the MCU
65
How can we measure calcium inside the mitochondria?
we need a sensor protein and a pre-sequence
66
What are 2 sensor proteins developed to measure the calcium inside the mitochondria?
photoproteins: emits light upon calcium binding and isolated from jellyfish GFP-based calcium sensors: composed of 2 fluorescent proteins (CFP and YFP) that are connected thanks to a bridge composed of calmodulin and M13 peptide
67
What is the MCU complex?
small protein of the IMM, which is aable to oligomerize
68
What is the MCU composed of?
many subunits (structural or gatekeepers)
69
What are the structural components of the MCU?
MCUb and EMRE
70
What are the gatekeepers of MCU?
MICU1 MicU2 MICU3 *act as regulators
71
What does the structural component of the MCU complex, MCUb act as?
dominant-negative subunit *this means it abolishes the overall activity of the complex
72
What is the distribution pattern of MCI and MCUb?
tightly regulated and tissue specific
73
The stoichiometry of MCU + MCUb establishes ____.
the magnitude of the uniporter permeability, which is tissue-specific.
74
Describe how the gatekeepers would work if the concentration of calcium is low:
MICU2 will interact with MICU1 to keep the channel closed
75
Describe how the gatekeepers would work if the concentration of calcium is high:
MICU1 will remove MICU2, which leads to the opening of the channell
76
What is MICU3 in regards to the type of activator?
MICU 3 is a positive regulator like MICU1
77
Why is calcium needed in the mitochondria?
calcium flux is needed to maximize ATP production
78
What is mitochondrial calcium overload?
it occurs when calcium conc. exceeds a certain threshold, which triggers the permeability transition
79
What does mitochondrial calcium overload lead to?
apoptosis because the excess of calcium opens the permeability transition pores located in the IMM
80
What to modes can the IMM pores act in?
both high and low conductance mode
81
What is a low conductance mode?
in physiological condition
82
at is a high conductance mode?
condition of cell damage
83
What happens in low conductance mode (physiological condition)?
pores open and close very fast and release small calcium waves outside the organelle *called flickering beacuse it gives the idea of periodic release from inside the cell to the outside
84
What happens in high conductance mode (cell damage)?
there is an alteration of the IM permeability that leads to apoptosis
85
What has been recently proposed i terms of mitochondrial permeability transition pores?
they could be composed of the aggregation of ATP synthase subunits

Molecular Cell Biology (10 decks)

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