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The role of mitochondrial DNA rearrangements in aging and human diseases

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Abstract

Instabilities and point mutations of the high molecular weight mitochondrial DNA (mtDNA) were shown to be correlated with various degenerative processes in both lower eukaryotes as well as in mammals. In filamentous fungi, circular and linear plasmids were demonstrated to be involved in mtDNA rearrangements and in the genetic control of senescence. In addition, in these eukaryotic microorganisms, which have proved to be ideal model systems in experimental gerontology, a number of nuclear genes were identified controlling the stability of the mitochondrial genome. Although the mitochondrial genome of mammals, including humans, appears to be quite stable in comparison to other species, mtDNA instabilities of the type described in fungi were observed in mitochondria of patients with different mitochondrial degenerative disorders (CPEO, KSS, Pearson syndrome, LHON, MERRF, MELAS). It was later demonstrated that such mtDNA rearrangements appear to accumulate progressively during aging in human subjects. These data suggest that instabilities of the mitochondrial genome may play an important role in the control of life span not only in lower eukaryotes, but also in humans. (Aging Clin. Exp. Res. 4: 273–286, 1992)

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Osiewacz, H.D., Hermanns, J. The role of mitochondrial DNA rearrangements in aging and human diseases. Aging Clin Exp Res 4, 273–286 (1992). https://doi.org/10.1007/BF03324108

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