Biochemical phenotypes associated with the mitochondrial ATP6 gene mutations at nt8993.

Two point mutations (T>G and T>C) at the same 8993 nucleotide of mitochondrial DNA (at comparable mutant load), affecting the ATPase 6 subunit of the F1F0-ATPase, result in neurological phenotypes of variable severity in humans. We have investigated mitochondrial function in lymphocytes from individuals carrying the 8993T>C mutation: the results were compared with data from five 8993T>G NARP (Neuropathy, Ataxia and Retinitis Pigmentosa) patients. Both 8993T>G and 8993T>C mutations led to energy deprivation and ROS overproduction. However, the relative contribution of the two pathogenic components is different depending on the mutation considered. The 8993T>G change mainly induces an energy deficiency, whereas the 8993T>C favours an increased ROS production. These results possibly highlight the different pathogenic mechanism generated by the two mutations at position 8993 and provide useful information to better characterize the biochemical role of the highly conserved Leu-156 in ATPase 6 subunit of the mitochondrial ATP synthase complex.

• Publication year

  2007

• Venue

  Biochimica et Biophysica Acta

• Publication date

  2007-07-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1016/J.BBABIO.2007.05.005PMID 17568559
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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