• Oxidative phosphorylation pathway most important
• 16.5 kB circular genome
• 13 genes the rest are tRNA molecules
• mostly coding material
• Coding material in outside heavy strand, little on inner light strand
• Requires nuclear proteins to replicate
• no recombination within genome

• 10-20X higher mutation rate than nuclear --> leads to high polymorphisms
• no proofreading
• no chromosomes
• stable DNA
• evolutionary genetic studies
• Disorder of mitochondria affect areas of high ATP usage

• Heteroplasmicity leads to passive segregation (can't tell which mito she will pass into egg)
• Higher muation freq more affected than lower
• Ragged red fiber --> mitos clump onto cell and show up in Gramori Stain, accumulates with age, not disease specific
• All diseases 1:10000
• Symptomatic overlap
• Symptoms exacerbated by major uses of ATP (exercise, etc)

• Point mutations in tRNA and rRNA
• Missense in coding region
• Rearrangements

Kearns-Sayre Syndrome

(Mito)

• Caused by single mtDNA deletions causing abnormal protein translation
• eye failure (pigment degeneration in retina, PEO)
• heart problems
• ataxia
• ragged red fibers
• hearing problems

• Caused by point mutation in tRNA lysine
• mito myopathy
• ataxia
• seizures
• hearing loss

MELAS

(Mito)

• Caused by point mutation in tRNA of leucine
• mito myopathy
• stroke-like episodes (initially reversible, progressively worse)
• vomiting
• hearing loss
• seizures

Lebers Hereditary Optic Neuropathy (LHON)

(Mito)

• Caused by missense mutation in Complex I
• midlife blindness
• affects males more than females
• Homoplasmic mutations --> all individuals come out as mutants

Genetic Testing for Mito Disorders

(Problems)

• Genotype/Phenotype Association
• Differences in Tissue Distribution
• Rare Mutations/Nuclear DNA Mutations
• Polymorphic Variation

• Segregation of mutation with phenotype
• heteroplasmy
• functional impairment
• phylogenetic conservation
• haplotype divergence of identical mutations