T2 L5, Mitochondrial myopathies

Question 1

How many Kb of mitochondrial DNA are there in the human genome?

Answer 1

16.5

Question 2

How are mitochondria inherited and why?

Answer 2

All from the mother because most sperm mitochondria are on the tail and that’s not absorbed on fertilisation. Paternal mitochondria that enter the egg are destroyed

Question 3

What 3 things does the mitochondrial genome code for?

Answer 3

13 respiratory chain proteins, 2 rRNA, and 22 tRNA

Question 4

Why does mitochondria efficiency decline with age?

Answer 4

Accumulation of damage and mutations to mtDNA caused by ROS. mtDNA suffers greatest exposure to ROS and is less effective in repairing DNA

Question 5

Name the 5 reactive oxygen species (ROS)

Answer 5

Superoxide anion (O2-), Hydroxyl radical (HO), Peroxide ion (O2 2-), Hydrogen peroxide (H2O2), and Hypochlorous acid (HOCl).

Question 6

What is SOD?

Answer 6

Superoxide dismutase

Question 7

What is the major producer of ROS?

Answer 7

The respiratory chain

Question 8

What’s another name for complex 5 in the e- transport chain?

Answer 8

ATP Synthase

Question 9

Give examples of tissues that are less tolerable of lowered ATP production

Answer 9

Neurones, myocytes, skeletal muscle cells, and beta-cells of the pancreas

Question 10

At cell division, how are mitochondria divided?

Answer 10

Randomly so not every cell will be diseased

Question 11

What is an Oocyte?

Answer 11

A cell in an ovary which may undergo meiotic division to form an ovum

Question 12

What does LHON stand for?

Answer 12

Lebers Hereditary Optic Neuropathy

Question 13

What does MERRF stand for?

Answer 13

Myoclonus Epilepsy with Ragged-Red Fibre

Question 14

What does MELAS stand for?

Answer 14

Mitochondrial Encephalomyopathy Lactic Acidosis and Stroke-like episodes

Question 15

What does KSS stand for?

Answer 15

Kearns-Sayre Syndrome

Question 16

What is LHON syndrome and what causes it?

Answer 16

A mutation affecting Complex I or Complex III that causes the mitochondria to have partially defective e- transport. Not enough e- is transported from succinate to support metabolism of neurones and this results in damage to the optic nerve and blindness

Question 17

What is MERRF syndrome and what causes it?

Answer 17

Causes a mutations on the tRNA for Lysine which disrupts synthesis of proteins essential for oxidative phosphorylation

Question 18

What is meant by ragged red fibres in MERRF?

Answer 18

The skeletal muscle fibres with MERRF have abnormally shaped mitochondria which clump up and accumulate. They will appear red after staining with Gomori modified Trichrome

Question 19

What is MELAS syndrome and what causes it?

Answer 19

A mutation affecting Complex I and primarily affects the brain and skeletal muscles. Symptoms will appear in childhood

Question 20

What are the childhood symptoms of MELAS syndrome?

Answer 20

Lactic acidosis, stroke-like episode with muscle weakness, seizures leading to loss of vision, and movement difficulties

Question 21

What is KSS and what causes it?

Answer 21

Caused by a 5kb deletion on the mt genome. Affected patients have short stature and often multiple endocrinopathies

Question 22

What are some symptoms of KSS?

Answer 22

Dementia, retinitis pigmentosa, lactic acidosis, heart conduction defects, and raised CSF protein content

Question 23

How are mitochondrial myopathies diagnosed?

Answer 23

Biochemical tests, histology, and genetic testing

Question 24

What therapies are there for those with mitochondrial myopthaies?

Answer 24

Physical therpay to increase muscle movement and vitamin therapies like riboflavin, creatine, CoQ, C, K, and carnitine

Question 25

Describe Mitochondrial gene replacement

Answer 25

Nuclei is transferred from the patient to a donated egg so the new egg has healthy mitochondria

Question 26

Describe maternal spindle transfer

Answer 26

This happens before fertilisation. The egg is reconstructed to contain only healthy mitochondria and is then fertilised and transferred into the womb