BS - Mitochondrial Disorders - Week 3 Flashcards
(37 cards)
Name 6 pieces of evidence of the endosymbiosis theory.
- Mitochondria and bacteria have simiar size and shape
- Mitochondria have 2 membranes, the outer is eukaryotic, the inner is prokaryotic (chemically)
- Mitochondria have circular DNA as do some bacteria (plasmids)
- Mitochondria contain prokaryotic ribosomes
- Mitochondria divide by binary fission, like bacteria
- Complex DNA repair mechanisms are missing from mitochondria
What is the energy efficiency of mitochondria?
70%
Which complexes are responsible for pumping H+?
Complexes I, III, and IV.
Where is the H+ gradient set up, and what is it used for?
Set up high in the intermembrane space, and used by ATPase to make ATP.
How many of mitochondrial proteins are encoded by mtDNA? What can be said of this regarding mutations?
Of over 1000 proteins, only 13 are encoded by mtDNA.
Therefore mutations to mtDNA are severe.
In what manner is mtDNA inherited?
Maternal inheritance
Compare the expression of mtDNA in females vs males.
Males - variable
Females - almost identical
In what 5 structures of the eye are mitochonria found in high density?
RGC NFL Plexiform layers Photoreceptors Optic nerve
Where in myelinated nerves are mitochondria typically found?
Limited to regions of the nodes of ranvier.
What 5 structures of the eye are typically affected by mitochondrial disease?
EOM Levator muscle Lens Retina Optic nerve
What are the two categories of mitochondrial disease? Describe what both mean.
Primary - direct impairment of mitochondrial functions by mutations in mtDNA or nDNA
Secondary - mitochondrial dysfunction resulting from either genetic or environmental factors
Name 6 examples of ocular complications as a result of mtDNA mutations.
Optic atrophy Optic neuropathy Ptosis Ophthalmoplegia Retinopathy Pigmentary retinopathy
Name the most common hereditary optic neuropathy, its prevalence, and whether it affects males or females more. Briefly describe what it is.
Dominant optic atrophy
1:12,000
Degenerative disorder, affecting RGCs and the NFL
Equally affects males and females
Name 3 clinical signs for dominant optic atrophy.
Saucerisation of the optic disc > 0.5 ratio
Peripapillary atrophy
Sectoral pallor of the optic nerve
The majority of dominant optic atrophy causes are due to what?
Mutations to nDNA encoded GTPase gene
What 3 complexes are affected in dominant optic atrophy?
Complex I, II, and III.
Describe Lebers hereditary optic neuropathy, including prognosis, number of eyes it affects, pain, and time taken to develop blindness.
Acute, bilateral, painless central vision loss over days to months.
What is the prevalence of lebers hereditary optic neuropathy, and does it affects males or females more?
1:25,000
Males 5x more affected than females
What are majority of Lebers hereditary optic neuropathy caused by?
3 mtDNA point mutations
What is the initial development lebers hereditary optic neuropathy?
Thickening of the RNF with disc pseudoedema and RGC loss
What are 4 factors affecting the severity of lebers hereditary optic neuropathy?
Nuclear genes
mtDNA genes
Environmental factors (smoking/alcohol)
Sex
Name 3 clinical signs of lebers hereditary optic neuropathy.
Disc hyperaemia
Telangi-ectatic (corkscrew) vessels
Relative opacity of the NFL
Name 2 means of further diagnostics for a suspected case of lebers hereditary optic neuropathy.
Family history of the disease
Gene testing
What is the onset of chronic progressive external ophthalmoplegia.
Childhood or up to 30s
