The role of mitochondria in ageing

Question 1

which energy substrate can be used by mitochondria to generate ATP?

Answer 1

pyruvate
palmitate
glutamine

Question 2

what does pyruvate dehydrogenase kinases do to pyruvate dehydrogenase complex?

Answer 2

inhibit it by phosphorylation

inhibit pyruvate entry into mitochondria

Question 3

which electron transport chain complexes generate superoxide radical?

Answer 3

complex I and III

Question 4

what are the main sources of energy?

Answer 4

carbohydrates - glucose
fats
protein - amino acids

Question 5

what is the key molecule generated by metabolism?

Answer 5

ATP

mostly generated in mitochondria

Question 6

mitochondria are

Answer 6

not static, can move

Question 7

pyruvate entry into mitochondria

Answer 7

pyruvate dehydrogenase complex has to be active which requires pyruvate dehydrogenase kinase to be inactive otherwise they phosphorylate the PD complex and prevent entry of pyruvate into the mitochondria

Question 8

PDK inhibitors

Answer 8

dichloroacetate

can reduce lactic acid build up as more pyruvate is forced into the mitochondria for oxidation

Question 9

how many mitochondrial complexes are there?

Answer 9

5

Question 10

complex I

Answer 10

NADH dehydrogenase

Question 11

Complex II

Answer 11

succinate dehydrogenase

Question 12

complex III

Answer 12

cytochrome C oxioreductase

Question 13

complex IV

Answer 13

cytochrome C oxidase

Question 14

complex V

Answer 14

ATP synthase

Question 15

what is the role of the mitochondrial complexes?

Answer 15

generating protons to build up proton gradient in intermembrane space

Question 16

important complexes in ageing

Answer 16

I and III due to ROS production - superoxide anion

Question 17

what are the ROS species?

Answer 17

O2
superoxide anion - O2-
peroxide - O2^2-
hydroxyl radical - OH radical
hydroxyl ion - OH-

Question 18

ROS

Answer 18

not always bad
used to kill pathogens - released from phagocytic cells
pancreatic insulin secretion requires some ROS signalling

Question 19

how can ROS be detoxified?

Answer 19

enzymatically

ROS scavengers

Question 20

what enzymes are involved in detoxifying ROS?

Answer 20

superoxide dismutase
catalase
Glutathione peroxidase

Question 21

superoxide dismutase

Answer 21

superoxide anion –> H2O2
zinc, copper and manganese versions
associated with familial motor neurone disease

Question 22

Catalase

Answer 22

H2O2 –> H2O

mainly expressed in peroxisomes

Question 23

glutathione peroxidase

Answer 23

H2O2 + reduced GSH (Glutathione) –> oxidised glutathione (GSSG) + H2O

Question 24

ROS scavengers

Answer 24

ascorbate
flavonoids
carotenoids

Question 25

mitochondrial genome

Answer 25

``` have their own circular DNA containing 37 genes in the mitochondria produces 2 ribosomal RNA 22tRNAs 13 polypeptides ```

Question 26

polypeptides produced by mitochondria

Answer 26

components of oxidative phosphorylation complexes | rely on nuclear genome projects because the polypeptides are large

Question 27

structure of complex I

Answer 27

largest nuclear and mitochondria DNA encoded subunits assembly proteins

Question 28

mutation in complex I

Answer 28

deficiency = Leigh disease/ sundrome | most common cause of mitochondrial deficiency

Question 29

structure of complex II

Answer 29

``` succinate dehydrogenase much smaller 4 subunits succinate dehydrogenase a-d A and B = soluble C and D = membrane bound ```

Question 30

mutations in complex II

Answer 30

leigh disease fatal genetic disease within 1 year of diagnosis cause cancer - shift towards glycolysis if there is a deficiency

Question 31

complex III structure

Answer 31

only 1 subunit comes from mitochondrial genome, rest from nucleus

Question 32

mutations of complex III

Answer 32

least common cause of mitochondrial disease | mutations lead to defects in liver, muscle, brain, heart and kidneys - high metabolic rate at rest

Question 33

structure of complex IV

Answer 33

13 subunits | 3 from mitochondria DNA and 10 nuclear

Question 34

what does complex IV do?

Answer 34

catalyses transfer of electrons to ferrocytochrome C to oxygen to generate water and build proton level up

Question 35

complex IV deficiency

Answer 35

1 of most important for energy production

Question 36

complex V role

Answer 36

FoF1 ATP synthase enzyme channel in mitochondrial membrane permeable to H+ to flow down concentration gradient causing a change in shape of ATP synthase, leading to ADP +Pi --> ATP

Question 37

structure of complex V

Answer 37

large | 30 subunits

Question 38

mitochondrial disease inheritance

Answer 38

fathers with mutant mitochondria do not pass on disease mothers with only mutant mitochondria will always pass on mutant mitochondria mothers with some mutant and some normal randomly pass on mutant mitochondria disease severity is proportional to % of mutant mitochondria someone has

Question 39

Hutchison-Gilford progeria syndrome

Answer 39

rare genetic disease accelerated ageing severe mitochondrial dysfunction

Question 40

normal ageing

Answer 40

complexes I and III generate ROS which cause oxidative damage to mitochondrial DNA - increasing risk of mutations mutations accumulate as ageing occurs causes mitochondria dysfunction and more ROS production normal ageing allows interaction of ROS with mitochondrial DNA

Question 41

Harman's free radical theory of ageing

Answer 41

mitochondrial genes get mutated over time

Question 42

age-dependent damage to mitochondria

Answer 42

generation of ROS normally cause stress response but if over time a mutation can cause a dysfunctional stress response and oxidative damage occurs

Question 43

disease

Answer 43

increases generation of ROS and accelerate ageing

Question 44

which complexes are least likely to be damaged by excess ROS?

Answer 44

complex III

Question 45

which mitochondrial complex is largest?

Answer 45

complex I