T2 L5, Mitochondrial myopathies Flashcards
How many Kb of mitochondrial DNA are there in the human genome?
16.5
How are mitochondria inherited and why?
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
What 3 things does the mitochondrial genome code for?
13 respiratory chain proteins, 2 rRNA, and 22 tRNA
Why does mitochondria efficiency decline with age?
Accumulation of damage and mutations to mtDNA caused by ROS. mtDNA suffers greatest exposure to ROS and is less effective in repairing DNA
Name the 5 reactive oxygen species (ROS)
Superoxide anion (O2-), Hydroxyl radical (HO), Peroxide ion (O2 2-), Hydrogen peroxide (H2O2), and Hypochlorous acid (HOCl).
What is SOD?
Superoxide dismutase
What is the major producer of ROS?
The respiratory chain
What’s another name for complex 5 in the e- transport chain?
ATP Synthase
Give examples of tissues that are less tolerable of lowered ATP production
Neurones, myocytes, skeletal muscle cells, and beta-cells of the pancreas
At cell division, how are mitochondria divided?
Randomly so not every cell will be diseased
What is an Oocyte?
A cell in an ovary which may undergo meiotic division to form an ovum
What does LHON stand for?
Lebers Hereditary Optic Neuropathy
What does MERRF stand for?
Myoclonus Epilepsy with Ragged-Red Fibre
What does MELAS stand for?
Mitochondrial Encephalomyopathy Lactic Acidosis and Stroke-like episodes
What does KSS stand for?
Kearns-Sayre Syndrome
What is LHON syndrome and what causes it?
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
What is MERRF syndrome and what causes it?
Causes a mutations on the tRNA for Lysine which disrupts synthesis of proteins essential for oxidative phosphorylation
What is meant by ragged red fibres in MERRF?
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
What is MELAS syndrome and what causes it?
A mutation affecting Complex I and primarily affects the brain and skeletal muscles. Symptoms will appear in childhood
What are the childhood symptoms of MELAS syndrome?
Lactic acidosis, stroke-like episode with muscle weakness, seizures leading to loss of vision, and movement difficulties
What is KSS and what causes it?
Caused by a 5kb deletion on the mt genome. Affected patients have short stature and often multiple endocrinopathies
What are some symptoms of KSS?
Dementia, retinitis pigmentosa, lactic acidosis, heart conduction defects, and raised CSF protein content
How are mitochondrial myopathies diagnosed?
Biochemical tests, histology, and genetic testing
What therapies are there for those with mitochondrial myopthaies?
Physical therpay to increase muscle movement and vitamin therapies like riboflavin, creatine, CoQ, C, K, and carnitine
Describe Mitochondrial gene replacement
Nuclei is transferred from the patient to a donated egg so the new egg has healthy mitochondria
Describe maternal spindle transfer
This happens before fertilisation. The egg is reconstructed to contain only healthy mitochondria and is then fertilised and transferred into the womb
