Abstract
The concept of mitochondrial disease was first described in 1962, in a patient with hypermetabolism of nonthyroid origin associated with defective mitochondrial coupling1 (reviewed by Luft 1994). Between 1960 and 1970, several clinical and histological descriptions of mitochondrial myopathies were published in the litterature. Using modified Gomori trichrome staining, Engel and Cunninghan (1963) identified irregular mitochondrial deposits on the muscle fibers of patient with myopathy, and called them ragged red fibers (RRF). After 1970, mitochondrial diseases were observed which affected tissues other than muscles, especially the central nervous system. Shapira et al. (1977) introduced the term of mitochondrial encephalomyopathy. From 1980, research made faster progress, and in 1987, a biochemical classification of the mitochondrial cytopathies was proposed (DiMauro et al. 1987), as follows: defects in transport, defects in substrate utilisation, defects in the Krebs cycle, defects in the respiratory chain, and defects in oxidation/phosphorylation coupling. The year 1988 saw the first descriptions of mtDNA deletions in mitochondrial myopathies (Holt et al. 1988), in the Kearns-Sayre syndrome (Lestienne and Ponsot 1988), and the first mtDNA point mutation in Leber’s hereditary optic neuropathy (Wallace et al. 1988). Almost all mtDNA — caused disorders depend on mutant gene dosage which is generally heteroplasmic with the normal mtDNA and functionally recessive. We will review here the main aspects of mtDNA alterations leading to respiratory chain impairments responsible for diseases.
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Lestienne, P., Bouzidi, M.F., Desguerre, I., Ponsot, G. (1999). Molecular Basis of Mitochondrial DNA Diseases. In: Lestienne, P. (eds) Mitochondrial Diseases. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-59884-5_4
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