Lecture 16 - mitochondria

Question 1

Mitochondrial Genome

Answer 1

•	Mitchondria have a separate genome
o	mtGenome encode several proteins, rRNAs, and tRNAs
	13 proteins, 2 rRNAs, 22 tRNAs
o	16,549 bp circular genome
o	Alternate genetic code
o	No introns
o	High mutation rate (100- 1000 fold nuclear rate)
o	About 10 copies per mitochondrion
o	100-1000s mitochondria per cell

Question 2

mtGenome Mutations

Answer 2

o Heteroplasmy – more than one species of mitochondrial DNA per cell
 Often results from high mtDNA mutation rate
 Contribute to variability in severity of disease
 leads to somatic mosaicism
o Homoplasmy – uniformity of mtDNAs
o Mutation deficits may be complemented by non mutated molecules
o Accumulate mitochondrial mutations w/ age
 Diseases may become more severe w/ age

Question 3

Mitochondrial mutation transmission

Answer 3

o Mitochondrial diseases exhibit maternal inheritance
o Sperm do no normally contribute mitochondria to zygote
 Children of affected males are not at risk
• 2 generation process from a mutated mtDNA to an affected individual
o Step 1 -partitioning of mitochondria
 partitioning of egg cytoplasm and mitochondria during early embryo cleavages may lead to a high level of mutated mitochondria in some blastomeres
o Step 2 – incorporation into germline
 Blastomere w/ mutated mitochondria becomes a primordial germ cell, then an oocyte. Oocyte is fertilized to become zygote. Resulting individual may be affected.

Question 4

Characteristics of Mitochondrial Diseases

Answer 4

o Mitochondrial disease are rare and exhibit maternal inheritance
o About 40 recognized diseases – all very rare
o Variable severity w/in affected families
o Affect tissues w/ high energy requirements (muscle&nerve)
o Childhood or adult onset
o Dx usually via muscle biopsy

Question 5

Leber’s Hereditary Optic Neuropathy (LHON)

Answer 5

o Mutation is respiratory chain enzyme NADH dehydrogenase (ND1-6)
o Rare: 1-2 in 500,000
o Degeneration of optic nerve leading to loss of central vision
o Affects males more frequently
o Usual onset in 20’s

Question 6

Myoclonic Epilepsy associated w/ ragged red fibers (MERRF)

Answer 6

 mutation in tRNA
 1 in 400,000
 Ataxia, epilepsy

Question 7

Myopathy, encephaly w/ lactic acidosis and stroke (MELAS)

Answer 7

 Mutations in mitochondrial tRNA
 Frequent late onset
 Muscle weakness, neurological deficits

Question 8

Kearns-Sayre Syndrome

Answer 8

o Young age of onset
o Usually deletion of mtDNA
o Paralysis of eye muscles, hearing loss