Mitochondria Flashcards

1
Q

What are the benefits of the symbiosis​?

A

A single bacterial cell can generate enough energy to sustain about 10000 genes.​

When the host cell acquired multiple oxidative bacteria, the bacterial energy could be pooled to provide the required energy could be pooled to provide the required energy for adding more genes to the host cell’s DNA to create more complex anatomical structures​.

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2
Q

What is the cost of gene expression​?

A

Whereas the energetic cost of possessing genes is trivial (2%), the cost of expressing them as protein (75%) is not and consumes most of cell’s energy budget.​

Mitochondria increased the number of proteins that cells can evolve, inherit and express by 4-6 orders of magnitude.​

​It still requires mitochondrial DNA​.

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3
Q

What do the mitochondria​ consist of?

A
  • Outer mitochondrial membrane​.
  • Intermembrane space (the space between the outer and inner membranes)​.
  • The inner mitochondrial membrane​.
  • The cristae (space formed by infoldings of the inner membrane)​.
  • The Matrix​.
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4
Q

What are the primary cellular functions of the mitochondria?

A
  • Supply energy to the cell in form of ATP.​​
  • Generate and regulate reactive oxygen species.​​
  • Buffer cytosolic calcium ions.​​
  • Regulate apoptosis through the mitochondrial permeability transition pore.​
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5
Q

What metabolic pathways take place in the mitochondria?

A
  • Electron transport chain – oxidative phosphorylation.​​
  • Tricarboxylic acid cycle or Krebs cycle.​​
  • Beta oxydation of fatty acids.​​
  • Gluconeogenesis.​​
  • Urea synthesis.​
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6
Q

What does the outer membrane contain?​

A

Contains numerous protein complexes including enzyme systems for metabolic steps and mitochondrial import protein complexes.​

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7
Q

What does the inner membrane contain?​

A

Contains the enzyme systems for partial fatty acid oxydation and the Electron Transport System (ETS).​

Contains protein complexes for protein import and export.​

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8
Q

What does the mitochondrial matrix contain?​

A
  • Contains the enzyme systems for the Krebs cycle and ketone metabolism.​
  • Contains the mitochondrial DNA (mtDNA).​
  • Contains quality control proteases and chaperones.​
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9
Q

What happens during glycolysis?

A
  • Glycolysis produces its energy 100 times faster than aerobic respiration.​
  • Glycolysis is the preferred energy source of rapidly growing cell populations.​
  • Glycolysis is important in early development – early zygote is highly dependent on glycolytic energy production as development progresses to he blastocyst stage.​
  • Glycolysis is predominant in dividing cells while oxydative phosphorylation dominates energy production in differentiated cells.​
  • Energetic shift from oxidative phosphorylation to glycolysis may correlate to disease (e.g. age related neurodegeneration, cancer – Warburg effect).​
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10
Q

What happens during the Krebs cycle?

A
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11
Q

What happens to mitochondrial NADH?

A

It gets oxidised by the electron transport chain, which pumps protons across a membrane and generates ATP through oxidative phosphorylation.

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12
Q

What is the role of FADH2?

A

To carry high-energy electrons used for oxidative phosphorylation.

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13
Q

What is the role of Coenzyme Q10?

A

It functions as an electron carrier from enzyme complex I and emzyme complex II to complex III.

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14
Q

What is the role of Cytochrome C?

A

It carries an electron in the ETC and is also an intermediate in apoptosis.

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15
Q

What is cardiolipin?

A

Cardiolipin is an important component of the inner mitochondrial membrane, where it constitutes about 20% of the total lipid composition. It can also be found in the membranes of most bacteria.

It regulates numerous enzyme activities.

Defects in cardiolipin can produce protein independant uncoupling.

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16
Q

What are the mechanisms of mitochondrial surveillance?​

A

Molecular quality control​

Chaperones and proteases:​

  • Protein folding​
  • Protein turnover​

Organellar quality control

Cellular quality control:

Apoptosis – cell death​

17
Q

What happens during the mitochondria Life Cycle?​

A
18
Q

How does mitochondrial DNA differ from the nuclear genome?​

A
  • Smaller number of genes.
  • Higher copy number.
  • Less effective repair mechanisms.
  • Higher mutation rates.
19
Q

What is the link between mitochondria and ROS?

A

More ROS production links to more mitochondria dysfunction.

Leads to oxidative damage, mtDNA mutations and ageing.

20
Q

What happens during the pathways of apoptosis?

A
21
Q

What are the causes of causes of Mitochondrial disease?​

A
  • Nuclear DNA mutation (inherited or acquired).​
  • Mitochondrial DNA mutation (inherited or acquired).​
  • Combined nuclear and mitochondrial DNA defects.​
  • Random occurences.​
22
Q

What are the differences between mtDNA and nuclear DNA mutations?​

A
23
Q

What is heteroplasmy?

A

Heteroplasmy is the presence of more than one type of organellar genome (mitochondrial DNA or plastid DNA) within a cell or individual.

It is an important factor in considering the severity of mitochondrial diseases.

Heteroplasmic cells divide and the mtDNA is distributed randomly to daughter cells resulting in skewed populations of wildtype or mutant mtDNA.

24
Q

What are the 2 classes of mtDNA variants created by mutations?

A

Single base pair variants
mtDNA rearrangements (deletions and insertions)

25
Q

What are primary mitochondrial diseases?

A

Diseases involving defects of oxidative phosphorylation.

26
Q

Give examples of clinical syndromes of mtDNA mutations:

A
  • Mental retardation
  • Migraine
  • Diabetes mellitus
  • Hypnotonia
  • GI dysmotility
  • Stroke
27
Q

What tests can be carried out to test for mitochondrial disease?

A
  • Muscle biopsy
  • Succinate dehydrogenase (SDH) stain
  • Cytochrome oxidase (COX) stain
  • Southern blot analysis
28
Q

What are the treatment principles?

A
  • Identify and treat nutritional deficiencies.
  • Avoid metabolic stressors.
  • Avoid extremes of heat and coldness.
  • Avoid unaccustomed strenuous exercise.
29
Q

What is Leigh’s syndrome?

A

Leigh syndrome is a severe neurological disorder that usually becomes apparent in the first year of life.

This condition is characterized by progressive loss of mental and movement abilities (psychomotor regression) and typically results in death within two to three years, usually due to respiratory failure.

A small number of individuals do not develop symptoms until adulthood or have symptoms that worsen more slowly.

30
Q

What diseases is the Krebs cycle linked to?

A
  • Fumarase (FH) deficiency.
  • Succinate dehydrogenase (SDH) deficiency.
  • Alpha-ketoglutarate deficiency.
  • Hyperlactatemia.
31
Q

What is meant by the Warburg effect?

A

The Warburg Effect is defined as an increase in the rate of glucose uptake and preferential production of lactate, even in the presence of oxygen. Each of these functions have been hypothesized to be the function of the Warburg Effect.

32
Q

What happens if damage to mitochondria is persistent?

A

If damage to mitochondria is persistent and defective mitochondria accumulate in the cell, it would lead to instability of the nuclear genome.​

Accumulated nuclear genome instability may help cells acquire new functions such as resistance to apoptosis, migration and invasive characteristics which in turn could induce tumorigenesis.​

Mitochondrial dysfunction appears to induce reversible or irreversible changes in the epigenotic landscape of nuclear DNA.

33
Q

What 3 factors contribute to Parkinson’s arising?

A
  • Aging​
  • Genetic susceptibility​
  • Environmental factors​
34
Q

What 2 pathways are dysfunctional in Parkinson’s disease?

A
  • Mitochondrial dysfunction​
  • Protein misfolding and aggregation​

Leads to increased ROS and decreased ATP production.