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PSIO303 Integrative Cellular Physiology > Block 1 - Mitochondria (L11-13) > Flashcards

Block 1 - Mitochondria (L11-13) Flashcards

1
Q

What are the two major roles of the mitochondria?

A

cellular respiration/ATP homeostasis

programmed cell death/apoptosis

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2
Q

What is the basic structure of a mitochondria?

A
  • rod shaped/round
  • two membranes
  • outer membrane is the boundary
  • inner membrane is folded into cristae that project inward
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3
Q

What are the three proteins in the inner membrane of the mitochondria?

A
  • electron transport chain molecules (NADH dehydrogenase, cytochrome b-c1, and cytochrome oxidase)
  • ATP synthase
  • Transport proteins
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4
Q

What is in the mitochondrial matrix?

A
  • enzymes for oxidation of pyruvate and fatty acids and use in citric acid cycle
  • mitochondrial DNA
  • mitochondrial ribosomes
  • tRNAs and enzymes needed for expression of the mitochondrial genes
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5
Q

What things do mitochondria and bacteria have in common?

A

circular DNA, double membrane, and similar electron transport chain

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6
Q

Mitochondria generate —– from —— for use in ——-.

A

generate energy from OxPhos for use in many pathways

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7
Q

Where does glycolysis occur?

A

cytoplasm, outside the mitochondria

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8
Q

Where does the Krebs/citric acid cycle occur?

A

inside the mitochondria

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9
Q

What drives ATP synthesis in the mitochondria?

A

NADH and FADH2 transport H+ protons into the intermembrane space (between the inner and outer membranes) via the electron transport chain

The proton gradient is used in chemiosmotic coupling to generate ATP

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10
Q

What is chemiosmotic coupling?

A

the process mitochondria use to harness energy

link between chemical bond-forming reactions that generate ATP and membrane transport

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11
Q

What are the two main steps of generating ATP in the mitochondria?

A
  1. electron transport chain shifts protons to create a gradient
  2. proton gradient is harnessed by ATP synthase to make ATP
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12
Q

What is the pathway leading up to ATP synthase

A

complex 1 - NADPH oxidase
complex 2 - succinate reductase
complex 3 - cytochrome bc1
complex 4 - cytochrome oxidase

NADH —> complex 1 —> Q
OR
succinate —–> complex 2 —–> Q
THEN
Q —> complex 3 —-> cytochrome c —-> complex 4

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13
Q

What is the final electron acceptor in the ETC?

A

oxygen

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14
Q

Is the plasma membrane voltage greater or less than the inner mitochondrial membrane voltage?

A

less than - the high protein gradient across the inner mitochondria creates a voltage that is much higher than the voltage across the plasma membrane

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15
Q

Where are ATP created, and how many?

A

glycolysis (2)
ox phos (34, but need O2)
= 36 ATP

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16
Q

A single cell consumes roughly —- ATP per second.

A

10 million

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17
Q

How many protons cause ATP synthase to spin once and generate 1 ATP?

A

10 protons = 1 spin = 1 ATP

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18
Q

Mitochondrial proton gradients are good sensors of…

A

cellular health

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19
Q

Mitochondria do not actually make new ATP, they…..

A

continually recycle ADP to ATP

20
Q

Why is ADP recycled instead of just making new ATP?

A

We would need 10 million molecules of ATP per second, or 60 kg ATP per day

That’s too much to make new every day, so we reuse throughout the day

21
Q

Does the citric acid/Krebs cycle generate ATP?

A

no, it makes precursors which are then used to make ATP

22
Q

Mitochondria can divide in a process called…

A

fission

23
Q

How do mitochondria get their proteins?

A

essential proteins that are coded by mtDNA are synthesized in the mitochondria
but MOST proteins are imported from the cytosol and are coded by nuclear DNA

24
Q

What happens to old/worn out mitochondria?

A

autophagy (phagocytosis of large particles):
- endoplasmic reticulum wraps around it
- fusion with a lysosomal vesicle
- mitochondrion is digested

25
Q

What happens to new mitochondria?

A

they can be transported around the cell by motor proteins along microtubules of the cytoskeleton

26
Q

Mitochondrial DNA, as opposed to nuclear DNA, is…

A

circular

27
Q

What is needed for proteins to be translocated into the mito?

A

translocation contact sites and specialized translocon structures are needed

TOM (translocon of the outer membrane)
TIM (translocon of the inner membrane)

28
Q

How do TOM and TIM work together to translocate proteins?

A
  • the cytosolic protein has a signal sequence on the end
  • signal sequence is recognized by TOM
  • TOM inserts the protein into the membrane, where it contacts TIM
  • TIM translocates the protein into the matrix of the mito
  • signal peptidase (inside the mito matrix) cleaves the signal sequence from the protein to create the mature mitochondrial protein
29
Q

Why is mito DNA inherited from the mother?

A

sperm has very few mito compared to the oocyte, and most are in the tail which does not even become part of the embryo

also, sperm mito may be programmed to die after fertilization

30
Q

What cytoskeletal element helps sperm swim?

A

microtubules (because the tail is a flagella)

31
Q

Why is mitochondrial inheritance risky business? Why is everything still okay though?

A

Risky: while nuclear genes are recombined every generation, mito DNA is passed asexually and therefore is 50x as prone to mutations

However: mito defects are so lethal that natural selection tends to prevent dysfunctional mito from establishing in a population

32
Q

What is heteroplasmy? Why is it able to happen in mito?

A

Heteroplasmy: a cell or tissue contains more than one type of mitochondrial genome

Each mitochondrion contains multiple copies of mtDNA, and a mutation does not necessarily affect all the copies, so some can be mutated while others are not. The dose of a mutation is important when considering the inheritance pattern of a mitochondrial disease.

33
Q

Besides energy homeostasis, what other functions do the mito have?

A
  • programmed cell death (apoptosis)
  • heat production
  • generation of reactive oxygen
  • calcium store
  • role in some diseases (impaired function from ntDNA mutations)
34
Q

What is apoptosis?

A

programmed cell death, orderly cellular self-destruction

about 100 thousand cells are produced every second, so 100 thousand also die every second by apoptosis

35
Q

Evolutionarily, why do cells undergo apoptosis?

A

bacteria evolved a mechanism to ensure that they died quickly when infected with a virus
this evolved into the mitochondrial pore which is part of the apoptosis machinery

36
Q

Describe the basic mechanism of mitochondrial apoptosis

A
  • the permeability transition pore opens and cytochrome c exits
  • cyt c activates Apaf-1
  • Apaf-1 activates caspases (family of proteases that begin the process of degrading cellular components)
37
Q

Where is cytochrome c located in the mito?

A

on the intermembrane space side of the inner membrane

38
Q

cytochrome c is crucial for apoptosis, but also…

A

the electron transport chain

39
Q

What are the stages of classic apoptosis?

A
  • healthy cell receives a death signal (extrinsic or intrinsic)
  • cell undergoes commitment to die (reversible)
  • cell is executed (irreversible) and condenses/crosslinks to become a dead cell
  • engulfment by macrophages and neighboring cells where it is degraded
40
Q

What role do mito play in glucose sensing/insulin release?

A
  • in pancreatic b cells, mito link glucose exposure to insulin release
    1. GLUT2 transporters introduce glucose to the cell, and mito increases the ATP:ADP ratio
    2. K+ gates close which depolarizes the cell
    3. voltage sensitive Ca++ channels open
    4. exocytosis of ins. storage granules to the bloodstream
41
Q

How are the B-cells impaired (causing loss of glucose-stimulated insulin release)?

A
  • superoxide radicals induce UCP-2 (uncoupling protein 2) upregulation
  • uncoupling causes proton leak, decreased ATP:ADP ratio, and loss of glucose stim. insulin release
42
Q

What are UCPs (uncoupling proteins)?

A
  • transmembrane proteins in mito that decrease the proton gradient generated in oxidative phosphorylation
  • they create a leak pathway that allows protons to cross the mito inner membrane, bypassing ATP synthase
  • basically, H+ gradient is uncoupled from ATP generation
43
Q

What is UCP1 vs. UCP2?

A

UCP1:
- brown adipose tissue
- babies and hibernating mammals
- diverts energy from ATP generation to thermogenesis (heat release) in response to cold
- decrease mito production of damaging reactive oxygen species

UCP2:
- white adipose tissue
- humans during feeding
- metabolic adaptation to fasting regardless of weight
- non-thermogenic uncoupling

44
Q

Mitochondrial mutation can cause disease in what systems?

A

nervous, cardiovascular, liver, kidneys, eyes, skeletal muscle, digestive, and pancreas

45
Q

How can a three person baby be made (in order to eliminate mito mutations)?

A
  • mother egg is enucleated
  • donor egg is enucleated
  • the nucleus of the mother’s egg is put into the enucleated donor egg with normal mito
  • sperm fertilizes that “new” egg
46
Q

When a three person baby is made, where does each part come from?

A

nucleus comes from mother, mito/rest of the egg comes from donor, sperm from father

PSIO303 Integrative Cellular Physiology (16 decks)

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