Mitochondria in ageing

Question 1

Which molecules can generate ATP

Answer 1

Pyruvate, palmitate and glutamine

Question 2

What does PDK1-4 do?

Answer 2

Inhibit PDC

Question 3

Which complexes generate superoxide radicals?

Answer 3

1 and 3

Question 4

Pyruvate entry to mitochondria

Answer 4

• Pyruvate dehydrogenase plays key role
• Pyruvate dehydrogenase kinase reduces pyruvate entry
• Dichloroacetate is PDK inhibitor

Question 5

Main role of complex I

Answer 5

NADH dehydrogenase

Question 6

Main role of complex 2

Answer 6

Succinate dehydrogenase

Question 7

Main role of complex 3

Answer 7

Cytochrome C oxidoreductase

Question 8

Main role of complex 4

Answer 8

Cytochrome C oxidase

Question 9

Main role of complex 5

Answer 9

ATP synthesis

Question 10

What do ROS do?

Answer 10

Kill pathogens

Pancreatic insulin secretion requires ROS secretion

Question 11

What are SODs?

Answer 11

zinc, copper (cytosolic/extracellular) and manganese (mitochondrial)

Question 12

What are catalases?

Answer 12

Expressed in peroxisomes

Question 13

What do glutathione peroxidase do?

Answer 13

Use reduced glutathione as a co-factor, producing oxidised glutathione

Question 14

What are the three ROS scavengers

Answer 14

Ascorbate, flavonoids, carotenoids

Question 15

Characteristics of mitochondrial genome

Answer 15

• Circular DNA molecule - double stranded
• 16,000 base pairs containing 27 genes
• 2x rRNA
• 22x tRNA
• 13 polypeptides
• Relies on nuclear genome for additional components

Question 16

Characteristics of complex 1

Answer 16

• Largest mitochondrial complex
• Nuclear and mitochondria DNA encoded
• Complex i deficiency = Leigh disease/syndrome

Question 17

Characteristics of complex 2

Answer 17

• Succinate dehydrogenase
• 4 sub-units - ABCD
• Heterotrimer
• A and B are soluble
• C and D are membrane bound
• Mutations = Leigh disease (fatal, neurodegenerative, diagnosed within 1 year of life)
• Mutations in B and D lead to tumorigenesis - glycolytic shift

Question 18

Characteristics of complex 3

Answer 18

• Least common deficiency
• 11 subunits but only 1 from mito genome
• Mutation = defects in liver, muscle, brain, heart and kidneys

Question 19

Characteristics of complex 4

Answer 19

• Cytochrome C oxidase
• 13 sub-units
• 3 sub-units from mito genome (COX 1,2,3)
• 10 sub-units from nuclear genome
• Catalyses transfer of electrons to ferrocytochrome C to oxygen = H2O production
• COX IV important for energy production

Question 20

Characteristics of complex 5

Answer 20

• Metabolism has so far generated H+ gradient across membrane
• Used for F0F1 ATP synthase - permeable to H+
• H+ flow down conc grad like wheel over water
• This changes shape of ATP synthase enzyme
• Powers pi + ADP
• 30 sub-units

Question 21

Mitochondrial inheritance

Answer 21

• Fathers don’t pass on mito DNA
• Mothers will pass on disease in DNA
• Mothers with some mutant and some normal can randomly pass on mutant DNA
• Disease severity is proportional to % mutant DNA

Question 22

How do mitochondria get damaged as we age?

Answer 22

• Complex 1 and 3 make superoxide radicals
• Leads to oxidative damage to DNA
• Older = more mutations
• Harman’s theory: mitochondrial genes get mutated over time - closer to source of ROS

Question 23

Which complex is least likely to be damaged by ROS and why?

Answer 23

3 - only 1 sub unit from mito DNA

Question 24

Which complex has most sub-units?

Answer 24

1

Question 25

Hutchinson-Gilford Progeria syndrome

Answer 25

Genetic condition looks like premature ageing

Slowed growth, narrow face