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 language | English |
|---|---|
| Pages (from-to) | 418-427 |
| Number of pages | 10 |
| Journal | American Journal of Human Genetics |
| Volume | 46 |
| Issue number | 3 |
| State | Published - Mar 1 1990 |
| Externally published | Yes |
Fingerprint
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 journal › Article
}
TY - JOUR
T1 - Transcription and translation of deleted mitochondrial genomes in Kearns-Sayre syndrome
T2 - Implications for pathogenesis
AU - Nakase, Hirofumi
AU - Moraes, Carlos T
AU - Rizzuto, Rosario
AU - Lombes, Anne
AU - DiMauro, Salvatore
AU - Schon, Eric A.
PY - 1990/3/1
Y1 - 1990/3/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0025373850&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0025373850&partnerID=8YFLogxK
M3 - Article
VL - 46
SP - 418
EP - 427
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
SN - 0002-9297
IS - 3
ER -