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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

Mitochondrial DNA expression in mitochondrial myopathies and coordinated expression of nuclear genes involved in ATP production.

The expression of nuclear and mitochondrial oxidative phosphorylation (OXPHOS) genes was examined in the skeletal muscle of patients with Kearns-Sayre syndrome (KSS), myoclonic epilepsy associated with ragged red fibers (MERRF), and myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) and compared with controls. In KSS muscle, mtDNA transcripts outside the deletion were elevated, while those within the deletion were reduced according to the percentage of deleted mtDNA molecules. In MERRF and MELAS muscle, mitochondrial transcripts levels were increased, but the increase was greater in MERRF muscle. The processing of mtDNA transcripts was reduced in all pathogenic muscles. This was true for full-length heavy and light strand transcripts as well as for the 16 S rRNA + tRNA(Leu)+ND1 transcript. However, the tRNA(Lys) level was reduced in all three muscles. In MELAS muscle, our results are not consistent with an impairment of transcription termination at the end of the 16 S mitochondrial rRNA. Finally, the transcription of the nuclear ATPsyn.beta and ANT1 genes was induced in parallel with the high level of mtDNA transcripts in MERRF and MELAS muscle, but was repressed in KSS muscle. The results demonstrate that the expression of nuclear and cytoplasmic OXPHOS genes is coordinated and that OXPHOS gene expression increases to compensate for respiratory deficiency. The repression of nuclear genes in KSS muscle could be a consequence of the segmental distribution of deleted mtDNA molecules in muscle cells.[1]

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