Over 100 pathogenic point mutations and 200 deletions, insertions, and rearrangements have been identified since the first mitochondrial DNA mutations were described in 1988. About 60% of the point mutations affect mitochondrial tRNAs, 35% affect polypeptide subunits of the respiratory chain, and 5% affect mitochondrial ribosomal RNAs. The clinical phenotypes of mitochondrial tRNA disease span the spectrum of all known oxidative phosphorylation disorders and include MELAS, MERRF, Leigh syndrome, PEO, deafness, diabetes, sideroblastic anemia, myoclonus, skeletal myopathy, cardiomyopathy, and renal tubular acidosis. Mutations in respiratory chain proteins encoded by mtDNA result in phenotypes ranging from exercise intolerance to blindness, ataxia, dystonia, dementia, and Leigh syndrome.
Conclusion: The primary disorders of oxidative phosphorylation are commonly associated with a delayed age of onset, organ selectivity, and an episodic, progressive course. Organ-specific, non-ATP related functions of mitochondria are discussed as important considerations in evaluating the pathogenesis of mitochondrial disease.