Transcription and translation of deleted mitochondrial genomes in Kearns-Sayre syndrome

Implications for pathogenesis

Hirofumi Nakase, Carlos T Moraes, Rosario Rizzuto, Anne Lombes, Salvatore DiMauro, Eric A. Schon

Research output: Contribution to journalArticle

118 Citations (Scopus)

Abstract

Large-scale deletions of human mitochondrial DNA (mtDNA) have been described in a clinical subgroup of mitochondrial encephalomyopathies associated with progressive external ophthalmoplegia and raggedred fibers in skeletal muscle, including cases of Kearns-Sayre syndrome (KSS). Since the decrease in the activities of mtDNA-encoded respiratory-chain enzymes did not seem to be correlated to the sites of the deletions, the role played by the mtDNA deletions in the pathogenesis of these disorders has been unclear. To address this issue, we studied transcription and translation of deleted mtDNA in two patients with KSS harboring two different deletions. We found that the deleted genomes were transcriptionally active in both cases. Analysis of translation in one of the patients showed that the "fusion" mRNA derived from the region spanning the deletion did not seem to be translated. Thus, the biochemical defects in KSS can be explained by a lack of translation of mtDNA-encoded respiratory-chain polypeptides in some mitochondria, which, in turn, is probably due to the lack of indispensable mtDNA-encoded tRNAs in these organelles. These results imply that deleted mtDNAs may be segregated from normal genomes in this group of diseases. It seems likely that the absence of translation in proliferating mitochondria containing partially deleted genomes plays a major role in the pathogenesis of these disorders.

Original languageEnglish
Pages (from-to)418-427
Number of pages10
JournalAmerican Journal of Human Genetics
Volume46
Issue number3
StatePublished - Mar 1 1990
Externally publishedYes

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Kearns-Sayre Syndrome
Mitochondrial Genome
Mitochondrial DNA
Genome
Electron Transport
Mitochondria
Mitochondrial Encephalomyopathies
Chronic Progressive External Ophthalmoplegia
Skeletal Muscle Fibers
Transfer RNA
Organelles
Messenger RNA
Peptides
Enzymes

ASJC Scopus subject areas

  • Genetics

Cite this

Transcription and translation of deleted mitochondrial genomes in Kearns-Sayre syndrome : Implications for pathogenesis. / Nakase, Hirofumi; Moraes, Carlos T; Rizzuto, Rosario; Lombes, Anne; DiMauro, Salvatore; Schon, Eric A.

In: American Journal of Human Genetics, Vol. 46, No. 3, 01.03.1990, p. 418-427.

Research output: Contribution to journalArticle

Nakase, Hirofumi ; Moraes, Carlos T ; Rizzuto, Rosario ; Lombes, Anne ; DiMauro, Salvatore ; Schon, Eric A. / Transcription and translation of deleted mitochondrial genomes in Kearns-Sayre syndrome : Implications for pathogenesis. In: American Journal of Human Genetics. 1990 ; Vol. 46, No. 3. pp. 418-427.
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