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M2M Unit IV > Mitochondria > Flashcards

Mitochondria Flashcards

1
Q

What is the principal source of energy for ATP in animal cells?

A

fatty acids and glucose

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2
Q

Where does glucose degradation occur?

A

Initially in the cytosol, then oxidative phosphorylation takes place in the mitochondria.

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3
Q

Describe the endosymbiont theory

A

A long, long time ago…
eukaryotic cells consumed a bacteria by endocytosis. The bacteria was capable of oxidative phosphorylation. Boom, don’t digest it, use it!
Inner membrane of mitochondria derived from bacteria, outer membrane from eukaryotic cell.

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4
Q

What volume of a cell is taken up by mitochondria?

A

Approximately 25% (lots of mitochondria in cell).

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5
Q

Describe mitochondrial membrane permeability

A

The outer membrane is semi-permeable.

The inner membrane is much less permeable.

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6
Q

Where is the machinery of the mitochondria located?

A

Inner membrane.

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7
Q

What are the folds of the inner membrane called?

A

Christae

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8
Q

What is the space inside the christae called?

A

Matrix

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9
Q

What is mitochondrial DNA?

A

DNA specific to the mitochondria, located in the matrix

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10
Q

Where are mitochondrial proteins synthesized?

A

Mostly in the cell cytoplasm, encoded by cellular DNA in the nucleus (not mitochondrial DNA in the matrix).

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11
Q

How are mitochondrial proteins imported to the matrix?

A 
First TOM (translocase of outer membrane), then TIM (translocase of inner membrane).
TOM transport is passive, while TIM transport is active and requires ATP.
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12
Q

What purpose do christae serve?

A

Increase surface area of the inner membrane

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13
Q

What process is required for mitophagy?

A

Fission

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14
Q

What process plays a key role in mitochondrial repair?

A

Fusion

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15
Q

What enzymes assist with mitochondrial fusion?

A

GTPases Mfn and OPA1

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16
Q

What enzymes assist with mitochondrial fission?

A

GTPases Fis1 and Drp

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17
Q

Where is the free energy that is released during oxidation of glucose stored?

A

NOT ATP! It’s in NADH.

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18
Q

What is NADH?

A

Nicotinamide adenine dinucleotide, a reducing coenzyme.

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19
Q

What are the reducing coenzymes?

A

NADH, FADH2

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20
Q

When do the reducing coenzymes NADH and FADH2 release their energetic electrons?

A

respiration

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21
Q

What is the receiver of high energy electrons in cellular respiration?

A

Oxygen. Oxygen takes the electrons and accompanying protons and transmogrifies into water. This water is known as metabolic water.

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22
Q

Where is the electron transport chain located?

A

Mitchondrial inner-membrane.

23
Q

How many protein complexes participate in the electron transport chain?

A

Four. They are cleverly named Complex I, Complex II, Complex III, and Complex IV

24
Q

Tell me more about Complex I-IV

A

Complex I = NADH dehydrogenase
Complex II = Succinate dehydrogenase
Complex III = Cytochrome bc1 complex
Complex IV = Cytochrome c oxidase

25
Q

What does the electron transport chain do?

A

Perform a series of redox reactions, which provide energy to pump protons from the matrix, across the inner membrane, into the intermembrane space.

26
Q

Which part of a mitochondria would you expect to be acidic?

A

Intermembrane space.

27
Q

What is the driving force for synthesizing ATP in mitochondria?

A

Electrochemical gradient provided by protons across the inner membrane.

28
Q

What is ATP synthase?

A

Protein complex on mitochondrial inner membrane that synthesizes ATP from ADP and Pi, using energy from proton gradient across the inner membrane.

29
Q

What are the components of ATP synthase?

A

F0 and F1 complexes. F0 spans the inner membrane, making a proton channel. F1 is bound to F0 and is the enzyme that actually synthesizes ATP.

30
Q

How many protons are required to flow across the inner membrane of the mitochondria to synthesize one ATP molecule from ADP and Pi?

A

3

31
Q

How does ATP get out of the matrix? And out of the mitochondria?

A

ATP-ADP translocase antiporter moves the molecules across the inner membrane. Presumably, the same protein is also on the outer membrane…

32
Q

Tell me about quinones

A

Quinones are lipid soluble electron carriers that shuttle electrons (and protons) between large, relatively immobile macromolecular complexes embedded in the membrane. Bacteria use ubiquinone (the same quinone that mitochondria use) and related quinones such as menaquinone. Another name for ubiquinone is Coenzyme Q10.

33
Q

How energy expensive is ATP-ADP translocase?

A

About 25% of energy produced by respiration goes to powering ATP-ADP translocase.

34
Q

What role do mitochondria play in cell death?

A

Mitochondria release cytochrome c into the cytoplasm, which complexes with several other proteins to form apoptosome, a cellular death signal.

35
Q

How is cytochrome c released from mitochondria?

A

Cellular damage induces Bak/Bax dependent permeabilization of mitochondrial outer membrane, releasing cytochrome c.

36
Q

What is apoptosome, and what does it do?

A

Apoptosome is formed as a complex of mitochondrial-sourced cytochrome c plus several cytoplasmic proteins that acts as a cellular death signal. Apoptosome activates caspases, which initiate apoptosis (regulated cell death).

37
Q

How do mitochondria respond to cellular ischemic injury?

A

Mitochondria promote necrotic cell death via MPTP-dependent permeabilization of the inner and outer mitochondria membranes, resulting in cytochrome release and elimination of any proton gradient.

38
Q

What happens to ATP in the absence of any proton gradient?

A

ATP production is blocked and ATP synthase is converted into ATPase, using up ATP. No ATP = necrosis.

39
Q

What can damaged mitochondria produce that is bad for a cell?

A

ROS - Reactive Oxygen Species

40
Q

What do unmanaged ROS do in a cell?

A

Oxidize cellular proteins, lipids, and DNA (think cancer!).

41
Q

How is mitochondria quality controlled?

A

1) Recognize and degrade misfolded proteins
2) Fix damaged mitochondria through fission/fusion with healthy mitochondria
3) Induce apoptotic cell death

42
Q

What molecules recognize misfolded or damaged mitochondrial proteins?

A

Several mitochondrial proteases such as mAAA, iAAA, and Lon recognize and degrade misfolded mitochondrial proteins.

43
Q

What is mitophagy?

A

Mitophagy is the process by which mitochondria are targeted for degradation via the autophagy pathway. Mitochondria are targeted for degradation when damaged by metabolic waste products, such as reactive oxygen species (ROS), or as a consequence of disease processes. Mitophagy is regulated by PINK1 and parkin protein. The occurrence of mitophagy is not limited to the damaged mitochondria but also involves undamaged ones.

44
Q

What does PINK1 do?

A

PTEN-induced putative kinase 1 (PINK1) is a mitochondrial serine/threonine-protein kinase encoded by the PINK1 gene. It is thought to protect cells from stress-induced mitochondrial dysfunction. PINK1 activity causes the parkin protein to bind to depolarized mitochondria to induce autophagy of those mitochondria. PINK1 is processed by healthy mitochondria and released to trigger neuron differentiation.

45
Q

What disease results from mutations in PINK1 gene?

A

Mutations in this gene cause one form of autosomal recessive early-onset Parkinson’s disease.

46
Q

What mitochondrial disease leads to Charcot-Marie-Tooth?

A

Neuropathy type 2A from mutation in Mfn2 gene (mitochondrial fusion machinery).

47
Q

What mitochondrial disease leads to autosomal dominant optic atrophy?

A

Mutation in OPA1 gene (mitochondrial fusion machinery).

48
Q

What mitochondrial disease leads to hereditary spastic paraplegia?

A

Mutation in mAAA protease

49
Q

Name three mitochondrial diseases and their mutational sources

A

Mfn2 gene -> Charcot-Marie-Tooth
OPA1 gene -> optic atrophy
mAAA protease -> hereditary spastic paraplegia

50
Q

What effect does arsenic have on mitochondria?

A

Potent toxin, inhibits oxidative phosphorylation (and hence ATP production).

51
Q

Name three mitochondrial functions

A

1) Generation of ATP
2) Apoptosis
3) Regulation of intracellular Ca ions

52
Q

How much energy is yielded by converting ATP to ADP?

A

About 7.3 kcal/mol

53
Q

What process accompanies mitochondrial fission?

A

Mitochondrial DNA replication

M2M Unit IV (10 decks)

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