Mitochondria Flashcards
(210 cards)
1
Q
How many membranes does mitochondria have?
A
2 - outer and inner
2
Q
Where are ATP synthases located?
A
inner membrane
3
Q
What is the equivalent to the cytoplasm in the mitochondria?
A
mitochondrial matrix
4
Q
The majority of proteins for mitochondria are encoded in ____
A
nuclear genome
5
Q
The mitochondria has ____ that code for itself
A
its own genome
6
Q
there are enzymes in the matrix that are involved in breakdown of what?
A
food products
7
Q
What is mitochondria known for?
A
ATP production - power plant
8
Q
ATP production is what kind of respiration?
A
Aerobic
9
Q
The number of mitochondria in a cell varies depending on what?
A
That cells energy needs.
10
Q
What kinds of cells have a lot of ATP?
A
neurons and muscle
11
Q
What is significant about the outer membrane of mitochondria?
A
It is permeable to ions
12
Q
What is significant about the inner membrane of mitochondria?
A
It is impermeable to ions
13
Q
What protein contributes to the impermeability of the inner membrane?
A
cardiolipin
14
Q
What is between the inner and outer membrane in mitochondria?
A
intermembranous space
15
Q
The matrix encodes for its own _____
A
ribosomes
16
Q
Where does actual ATP production occur?
A
matrix
17
Q
What important reactions happen in the mitochondria inner membrane?
A
ETC, ATP synthesis (the actual production of ATP occurs in matrix)
18
Q
Oxidative metabolism is the production of ____
A
ATP
19
Q
What important synthesis happens in outer membrane of mitochondria?
A
Cardiolipin synthesis
20
Q
Where are TCA cycle enzymes located?
A
matrix of mitochondria
21
Q
What allows for the free diffusion of ions in outer membrane of mitochondria?
A
Porins
22
Q
Where do transmembrane proteins cross in mitochondria?
A
Outer & inner membrane
23
Q
Where is peptidoglycan located in mitochondria?
A
intermembranous space
24
Q
What is a double phospholipid?
A
Has four fatty acid tails
25
A cardiolipid is a ____
phospholipid
26
Where is cardiolipid made?
Mitochondria
27
Key words: cardiolipin synthesis, SIDS, high mortality in infants are what disease?
Barth syndrome
28
Defect in cardiolipin is the cause of what disease?
Barth syndrome
29
What is the mode of inheritance for barth syndrome?
x-linked
30
Characteristics: SIDS, cardiomyopathy, generalized muscle weakness, chronic fatigue, neutropenia are what disease?
Barth syndrome
31
What is neutropenia?
abnormally low concentration of neutrophils in blood
32
What is the mechanism for Barth syndrome?
defect in cardiolipid -cardiolipid helps create impermeability of inner membrane in mitochondria → lack of structure & permeability → inefficient ATP synthesis → chronic fatigue
33
Where does glycolysis take place?
cytoplasm
34
What does glycolysis become?
pyruvate
35
Without oxygen, pyruvate goes through what?
fermentation
36
With oxygen, pyruvate goes through what reaction?
oxidative phosphorylation
37
What is pyruvate broken down to in mitochondria?
Acetyl CoA
38
How is the first proton pumped into the intermembranous space in the ETC?
NADH has a high energy electron, complex I has higher affinity for electron than NADH, with the coupling of electron a proton is released into inter membranous space
39
How many complexes are there in the ETC?
4
40
Each time an electron is passed from one carrier to the next in the ETC, what happens?
a proton is pumped into intermembranous space
41
Why are protons pumped into intermembranous space in ETC?
to create a proton gradient, want a much higher concentration of protons outside of matrix
42
How can protons enter into matrix of mitochondria?
ATP synthase
43
How is acetyl CoA metabolised?
By TCA, reduces NAD+ to NADH
44
What is used to pass high energy electrons to first complex in ETC?
NADH
45
When proton enters the cell through ATP synthase, what allows that process to create ATP?
mechanical energy rotates enzyme and uses that energy to couple ADP and inorganic phosphate to make ATP
46
Once ATP is made in mitochondria, what happens to it?
It is exported to cytoplasm for use
47
Why is it called oxidative phosphorylation?
oxidation: generating high energy electrons
phosphorylation: the electrons are used to couple ADP to inorganic phosphate to create ATP
48
What is the gradient across the inner and intermembrane space called?
electrochemical proton gradient
49
Why is it called the electrochemical proton gradient?
Chemical: the intermembrous space has lower pH b/c of all the protons
electro: charge is more positive in intermembrous space
50
What drives ATP synthesis?
Electrochemical proton gradient
51
What does the proton couple with at the end of the ETC?
Oxygen - makes water
52
Where is the proton carrier located in ATP synthase?
transmembrane
53
Where is the head located in ATP synthase?
matrix
54
What does the head do in ATP synthase?
binds ADP to inorganic phosphate, it does this via rotation and conformation change
55
How does the head attach ADP to inorganic phosphate (Pi) in ATP synthase?
rotation and conformational change
56
What does ATP synthase do?
couples oxidation to phosphorylation
57
What assists ATP in leaving the mitochondria and going to the cytoplasm?
mitochondrial gradient (there is different pH and voltage gradient)
58
What does the TCA cycle create?
CO2 & NADH
59
How do the concentrations of ions in cytoplasm and intermembranous space of mitochondria compare?
They are similar
60
Protons fall down ______ ______ through ATP synthase, making ATP
electrochemical gradient
61
What is the exception to the way mitochondria make ATP?
thermogenesis - brown fat
62
What do the TCA and ETC produce in brown fat?
heat
63
What does UCP stand for?
uncoupling protein
64
What is another name for uncoupling protein?
thermogenin
65
What does thermogenin do?
It uncouples oxidation from phosphorylation to make heat
| it allows protons to "leak " from cytoplasm to matrix
66
Electrons have a very high affinity for what?
Oxygen
67
What happens when an electron reacts with oxygen?
Free radical (reactive oxygen species)
68
There is high probability of what bad thing happening in mitochondria?
free radicals being created
69
What does ROS stand for?
reactive oxygen species
70
ROS is very damaging to what?
ETC, protein, DNA, RNA
71
Why is ROS in mitochondria so dangerous compared to say, a ROS in nucleus?
mitochondrial genome does not have repair mechanisms that are in place in nucleus
72
Mutations in mitochondrial genes will affect what?
ETC
73
Explain how ROS can lead to snowball affect
More ROS leads to more damage of DNA, ETC, etc. the more damaged the DNA & ETC is, the more ROS is created, and the cycle continues
74
What is the function of superoxide dismutase?
It converts ROS to hydrogen peroxide
75
What is the function of glutathione peroxidase?
converts hydrogen peroxide to water
76
What does SOD2 stand for?
superoxide dismutase
77
What does GPX stand for?
glutathione peroxidase
78
Describe the extrinsic pathway for apoptosis
Cell: death receptor → death ligand binds death receptor → recruits proteins → activate caspase →activates more caspases →digest cell→ scramblase inhibitor broken down → scramblase puts phosphotidyl serine on outside
79
Describe the intrinsic pathway for apoptosis in mitochondria
DNA damage → opening of pores in outer membrane of mitochondria → cytochrome C leaks to cytoplasm → cytochrome C combines w/ cytosolic protein Apaf1 → activates caspases → cell death
80
What is caspase important for?
apoptosis
81
Bcl-2 is a family of proteins that control what?
control pore formation in mitochondria
82
What do pro-apoptotic bcl-2 proteins do?
promote pore formation in mitochondria
83
Pore formation in mitochondria promotes what?
apoptosis
84
What do anti-apoptocic bcl-2 proteins do?
inhibit the pro-apoptotic bcl-2 proteins, which stop apoptosis
85
BAX & BAD are examples of what?
pro-apoptotic bcl-2 proteins
86
What does Bcl-2 inhibit?
BAX
87
Bcl-2 is what kind of protein?
anti-apoptotic
88
Cytochrome C in cytosol activates what for apoptosis?
caspase cascade
89
How do mitochondria replicate/divide?
lengthen and then go through fission (similar to bacteria)
90
Explain the bottleneck affect in mitochondria
There are lots of mitochondria, but only a few are taken to create an egg. The egg could have all normal cells, all mutant cells, or any combination. Depending on the mitochondria in the egg, and then how that replicates, will determine if child will express disease
91
What is heteroplasmy?
Variability of mitochondrial diseases. can't say recessive or dominnat b/c of all the mitochondria in cell.
92
What is homoplasmy?
All mitochondria are the same - can be wild type or mutant (almost all homoplasmy mutants will die)
93
How does mitotic segregation affect the way wild type and mutant mitochondria divide and affect a child?
Certain cells can end up having way more mutant mitochondria than others, and certain tissues can be more affected than others
94
What cells are most affected by mitochondrial inheritance?
muscle & neuron
95
What does mRNA have to have to enter mitochondria?
mitochondrial signal sequence
96
Where are mRNA that are destined to mitochondria folded?
In mitochondria
97
What is the purpose of Hsp70?
Prevents mitochondrial protein from folding in cytoplasm
98
Where are Hsp70 proteins located?
In cytoplasm and matrix of mitochondria. They have different functions in both locations. in cytoplasm prevents folding of protein, in mitochondria it helps fold protein
99
What is TOM?
A protein in outer membrane of mitochondria that Hsp70 will bind to
100
What happens once Hsp70 binds to TOM?
the unfolded protein travels across membrane, signal sequence is removed by protease, protein spontaneously folds or is helped by Hsp60
101
What does TOM stand for?
translocase of outer membrane
102
What helps protein fold in mitochondria?
Hsp60
103
How many proteins are encoded for in mitochondria?
13
104
How many total genes are in mitochondrial DNA?
37
105
How many tRNA genes are in mitochondrial DNA?
22
106
How many rRNA genes are in mitochondrial DNA?
2
107
What are the two strands of the mitochondrial genome called?
H-strand & L-strand
108
H-strand is rich in what?
G
109
L-strand is rich in what?
C
110
How many genes are encoded for in H strand?
12 of the protein - coding genes
111
How many genes are encoded for in L-strand?
1 protein coding gene (and some tRNA)
112
What controls the replication and transcription of mitochondrial DNA?
D loop
113
What does D loop stand for?
Displacement Loop
114
How many origins of replication are there no the mitochondrial genome?
2
115
How are mitochondrial strands transcribed?
polycistronically (at the same time)
116
Which is the heavy mitochondrial strand?
H-strand
117
Which is the light mitochondrial strand?
L-strand
118
What is the promoter for the heavy strand?
HSP
119
What is the promoter for the light strand?
LSP
120
How are the promoter regions for the two mitochondrial strands related to each other?
H promoter (Oh) is at twelve o clock, L promoter (OL) is at 8 o clock
121
Which complex in ox phos pathway contains only nuclear-encoded proteins?
Complex II
122
Complex I contains how many genes encoded for by mitochondria?
7
123
Complex III contains how many genes encoded for by mitochondria?
1
124
Complex IV contains how many genes encoded for by mitochondria?
3
125
Complex V contains how many genes encoded for by mitochondria?
2
126
What surrounds every protein coding gene in mitochondrial genome?
tRNA coding genes
127
What is one purpose of tRNA coding genes in mitochondrial genome?
Act as spacers b/w different genes
128
Which complexes in mitochondria carry out oxidative phosphorylation?
I, III, IV
129
Replication occurs _____ for mitochondrial DNA (symmetric or not?)
Asymmetrically
130
To complete replication, mtDNA has its own ____ and ____
polymerase and helicase
131
One cell may contain how many mtDNA genomes?
thousands
132
Are there okazaki fragments in mtDNA replication?
no
133
What is the dedicated helicase for mtDNA called?
Twinkle
134
How many mitochondrial DNA polymerase are there?
1
135
What is the name of the mitochondrial DNA polymerase?
DNA polymerase gamma
136
What is the function of DNA polymerase gamma?
mostly replication, some repair
137
What does the PLOG gene encode?
Catalytic subunit
138
Mutations in PLOG are associated with what?
reduced levels of mtDNA and/or mutations in the mtDNA
139
What is Ophtalmoplegia?
Weakness or paralysis of muscles that move the eye
140
Key words: bilateral ptosis, mtDNA depletion/deletion, polymerase gamma are what disease?
Progressive External Ophtalmoplegia (PEO)
141
PEO stands for what?
Progressive External Ophtalmoplegia (PEO)
142
Characteristics: Bilateral ptosis – progressive weakening of external eye muscles, proximal muscle weakness and wasting, exercise intolerance are what disease?
PEO - Progressive External Opthalmoplegia
143
What is the most common mode of inheritance for PEO?
Autosomal dominant, but can be autosomal recessive
144
How many genes are involved in PEO disease?
5
145
If PLOG or TWINKLE is the mutated in PEO disease, what is the mode of inheritance?
AD
146
What is the mechanism for PEO?
mtDNA depletion or large deletion - usually is large deletion
147
What two proteins may affected by mutations in PEO?
Twinkle & PLOG
148
What kind of mutation is more damaging to the mtDNA and will have more sever clinical outcomes?
Missense mutations
149
What is the name of a nucleoside used to treat HIV?
AZT
150
Describe AZT
A nucleoside used to treat HIV. It is thymidine analogue - has thymidine without hydroxyl group at 3' and with a bunch of nitrogens at 2'
151
What is Zidovudine?
Another name for AZT - drug used to treat HIV
152
What is the mechanism AZT/Zidovudine works?
It doesn't affect DNA Pol delta (in nucleus) but DNA Pol gamma (in mitochondria) is inhibited. B/c it is attached to methylated thymine, thymine will insert itself onto mtDNA and cause deletion of DNA. It protects against HIV because it competes with dTTP for incorporation into DNA by viral reverse transcriptase
153
What is myopathy?
disease of muscle
154
What is a side effect of AZT?
Myopathy
155
What are the names of the two promoters in control region of mtDNA?
HSP & LSP
156
What processes the giant transcripts from mitochondria?
RNA endonuclease
157
What does RNA endonuclease recognize in the mitochondria to excise certain genes?
It recognizes secondary structure in tRNA of the giant transcripts
158
mRNAs in mitochondria are ______ but not _____
poly adenylated but not capped
159
How does protein synthesis in mitochondria resemble that of bacteria?
It starts with N-formyl methionine
160
Which has more repeats, nuclear or mitochondrial DNA?
nuclear
161
How many tRNAs are involved in mitochondrial translation?
22
162
Explain the difference b/w tRNA in mitochondria and the rest of the cell
There is more wobble in tRNA in mitochondria, there is less tRNA available to recognize all the codons
163
What is the exception to the universal genetic code? Give example
Mitochondria codons do not code for the same thing as codons for everything else. Ex: UGA is usually stop codon, in mitochondria it codes for Trp
164
What is the size of the nuclear genome compared to mitochondrial?
Nuclear: 3 billion bp
Mitochondrial: 16 thousand bp
165
Are there introns in mitochondrial DNA?
No
166
Compare the % of coding DNA in nuclear genome vs. mitochondrial
Nuclear: 3%
Mitochondrial: 93%
167
What is the mutation rate of mitochondrial DNA? Why?
10x faster than in nuclear DNA. b/c of oxygen radicals formed after ox/phos
168
Mitochondrial DNA is very variable, meaning it is _____
polymorphic
169
Why is mtDNA so polymorphic?
the high mutation rate
170
The variations in mtDNA are mostly what?
SNP's (single nucleotide polymorphism) & small deletions/insertions
171
What are the 3 major types of mutations in mtDNA?
deletions or duplications
point mutations in tRNA
Missense mutations in coding regions
172
What do most mtDNA mutations affect
ox/phos - ultimately ATP production
173
Describe a ragged red muscle fibers
It has defective mitochondria, so more mitochondria are produced. If you biopsy and stain with certain dye, it will look ragged and stain red, it has a lot more mitochondria.
174
What is the threshold hypothesis for mtDNA disorders?
the proportion of mutated mtDNA molecules must exceed a certain threshold before clinical consequences
175
Mitochondrial diseases often exhibit what?
reduced penetrance
176
The _____ of consequence of mitochondrial mutations correlates with _____ of mutated molecules
severity, proportion
177
People can survive giant mutations in mtDNA but not if it's ______
homoplasmic
178
Giant deletions are usually inherited how?
Spontaneously - not passed down
179
A giant deletion is easy to detect using what method?
southern blot
180
How will a giant deletion present on a southern blot compared to a normal mitochondrial DNA?
normal will have one blot. Mutated will have 3, because of the deletion. They will be thicker b/c there is more mitochondria b/c cell is compensating for it not working well
181
The ____/______ of bottleneck with oocytes can cause very different levels of heteroplasmy in children
restriction/ampmlification
182
key words: no bone marrow involvement, late onset, ragged red fibers are what disease?
Kearns-Sayre Syndrome (KSS)
183
KSS stands for?
Kearns-Sayre Syndrome
184
Characteristics: late onset, typical ragged red fibers (>80% mutated mtDNA), PEO, retinopathy, cerebellar ataxia, heart block are what disease?
Kearns-Sayre Syndrome
185
What is the mode of inheritance for KSS?
mitochondrial
186
What is the mechanism for KSS?
giant mtDNA deletion
187
What does MELAS stand for?
Mitochondrial Encephalomyopathy, Lactic Acidosis and Stroke-like episodes
188
What is mutated in MELAS?
leucine tRNA
189
Key words: tRNALeu, short, stroke, diabetes are what disease?
MELAS
190
Characteristics: short stature, stroke-like episodes (vomiting, headaches, visual disturbances), diabetes, sensorineural hearing loss are what disease?
MELAS
191
MELAS is always what?
heteroplasmic
192
key words: tRNALys, ragged red fibers, epilepsy are what disease?
MERRF
193
characteristics progressive myoclonic epilepsy and seizures are what disease?
MERRF
194
MERRF stands for?
Myoclous Epilepsy and Ragged Red Fibers
195
MERRF is always
heteroplasmic
196
What is the mutated gene in MERRF?
lysine tRNA
197
What does LHON stand for?
Leber's Hereditary Optic Neuropathy
198
What is the only mitochondrial disease that might be homoplasmic?
LHON
199
What kind of gene mutation is in LHON?
missense
200
key words: mutated Complex I gene, optic nerve damage, homoplasmy, bilateral vision failure are what disease?
LHON
201
characteristics: subacute painless bilateral visual failure, male:female 4:1 (X-chromosome penetrance), ~24 years old are what disease?
LHON
202
What complex is affected in LHON?
Complex 1
203
key words: ATPase 6 gene, ataxia, retinopathy, pigmentation, Leigh Syndrome Note: Maternally inherited Leigh Syndrome is a more severe form with a larger portion of mutated mtDNA are what disease?
NARP
204
characteristics: late childhood or adult onset peripheral neuropathy, ataxia, pigmentary retinopathy are what disease?
NARP
205
NARP is always
heteroplasmic
206
What does NARP stand for?
Neurogenic muscle weakness, Ataxia, and Retinitis Pigmentosa
207
What kind of mutation is in NARP?
missense
208
what gene is mutated in NARP?
ATPase 6 gene of Complex V
209
NARP is a ____variation of Leigh syndrome
milder
210
Describe 3 parent babies
mother with affect mtDNA can have unaffected children, nuclear genome of affected zygote transferred to another zygote from unaffected donor.
