Origin of MitochondriaOrigin of MitochondriaEndosymbiont TheoryEndosymbiont Theory
• Similar size to certain free-living bacteria
• Similar chromosome & cytoplasm to bacteria
• Similar ribosomes to bacteria
• Similar cell division to bacteria
• Independent replication & gene expression
Nuclear (Cellular) ChromosomesNuclear (Cellular) Chromosomes
3.2 billion total nucleotide pairs3.2 billion total nucleotide pairs
MitochondrialMitochondrialChromosomesChromosomes
2-10 @ per mito2-10 @ per mito1000-10000 per cell1000-10000 per cell
0.32-1.6 billion0.32-1.6 billion total nucleotide pairstotal nucleotide pairs
Genetically Genetically Controlled Controlled ProcessesProcesses
in Mitochondriain Mitochondria
• 13 genes for respiratory chain proteins• Subunits of the ATPase complex
• Subunits for the NADH-dehydrogenase complex
• 22 genes for tRNAs
• 2 genes for rRNAs
• Maintenance of cellular energy levels
Human Mitochondria
• 2-10 chromos per mito• 13 protein-encoding regions• 3 subunits of cytochrome c oxidase
complex• Cytochrome b complex• 2 subunits of the ATPase complex• 60% occupied by six subunits of
NADH dehydrogenase complex• 22 tRNAs• 2 rRNAs• other
Stability of Mitochondrial DNAStability of Mitochondrial DNA
• Mutatation rate 10X higher than nuclear DNA
• Mutations generated by oxidation by-products
• No protective histones
• Ineffective DNA repair
• Typically point mutations or deletions
• Tolerance for deletions variable
• Some deletions recurring in unrelated patients
Mitochondrial DiseasesMitochondrial DiseasesGeneral CharacteristicsGeneral Characteristics
• Penetrance usually complete (100%)• Expressivity highly variable• Age of onset variable• Frequently limited to specific tissues• Usually appear as reduced muscle strength
together with degeneration of other tissues• Affects organs with high energy requirements:
brain, heart, skeletal muscle, eye, ear, liver, pancreas, and kidney
Some Mitochondrial DiseasesSome Mitochondrial Diseases
• Kearns-Sayre syndromeopthalmoplegia, retinal degeneration, cardiomyopathy
• Lactic-Acidosis-Encephalomyopathy-Stroke syndrome
• Neurogenic muscle weakness with ataxia and retinitis pigmentosa syndrome
• Pearson syndromebone marrow and pancreas failure
• Diabetes-deafness syndrome
Mitochondrial DiseasesMitochondrial DiseasesGeneral CharacteristicsGeneral Characteristics
• Penetrance usually complete (100%)• Expressivity highly variable• Age of onset variable• Frequently limited to specific tissues• Usually appear as reduced muscle strength
together with degeneration of other tissues• Affects organs with high energy requirements:
brain, heart, skeletal muscle, eye, ear, liver, pancreas, and kidney