title: Mitochondrial diseases.
abstract: With the discovery of mitochondrial DNA (mtDNA) mutations in different neuromuscular disorders, investigations now seek to clarify how the mutant mtDNA induces biochemical and morphologic defects. In one of the most important approaches human mutant mtDNA is transferred into cells that lack mtDNA to examine the relationship between the amount of mutant mtDNA and defects in cell growth, respiration and enzyme activities. The resulting cells are 'cybrids'; these clonal cells contain the heteroplasmic mutant and normal mtDNA from patients with mitochondrial diseases. The mitochondria become functionally defective when the amount of mutant mtDNA exceeds a certain threshold, which differs from mutation to mutation: 60 to 70% in chronic progressive external ophthalmoplegia (CPEO) and probably 95% in the syndromes of mitochondrial encephalopathy, myopathy, lactic acidosis, and stroke-like episodes (MELAS), and myoclonic epilepsy with ragged red fibers (MERRF). This threshold effect may explain the tissue-specific patterns of clinical expression.
authors.affiliation: Division of Ultrastructural Research, National Center of Neurology and Psychiatry (NCNP), Toyko, Japan.
authors.forename: I
authors.initials: I
authors.lastname: Nonaka
mesh_terms: D002872:Chromosome Deletion; D004272:DNA, Mitochondrial / Q000235:genetics*; D006801:Humans; D017241:MELAS Syndrome / Q000235:genetics; D017243:MERRF Syndrome / Q000235:genetics; D017237:Mitochondrial Encephalomyopathies / Q000235:genetics*; D017240:Mitochondrial Myopathies / Q000235:genetics*; D017246:Ophthalmoplegia, Chronic Progressive External / Q000235:genetics; D015418:Optic Atrophies, Hereditary / Q000235:genetics; D017354:Point Mutation / Q000235:genetics; D016133:Polymerase Chain Reaction
chemical_list: D004272:DNA, Mitochondrial