Mutations in subunit 6 of the F1F0-ATP synthase cause two entirely different diseases.

Abstract

A lowered efficiency of oxidative phosphorylation was recently found in a Leber hereditary optic neuropathy (LHON) proband carrying a mutation in the mtDNA gene for subunit 6 of the membrane-bound F0 segment of the F1F0-ATP synthase [9]. This phenotype was transferred to cytoplasmic hybrid cells together with the mutation, proving its functional significance. Increasing the respiratory rate in the mitochondria from this mutant raised the ATP/2e- ratio back to normal values. A different mutation in the same mtDNA gene has been found in patients with the NARP syndrome [10]. Although the ATP/2e- ratio is also decreased in this mutant, in this case an increase in the respiratory rate could not compensate for it. Whilst both mutations affect subunit 6 of the proton-translocating F0 segment, the LHON mutation induces a proton leak whereas the NARP mutation blocks proton translocation. Hence, the latter will have much more destructive metabolic consequences in agreement with the large clinical differences between the two diseases.

• Authors: A Majander, T Lamminen, V Juvonen, P Aula, E Nikoskelainen, M L Savontaus, M Wikström
• Journal: FEBS letters (FEBS Lett) Vol. 412 Issue 2 Pg. 351-4 (Jul 28 1997) ISSN: 0014-5793 [Print] England
• PMID: 9256250 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DNA, Mitochondrial
• Adenosine Triphosphate
• Proton-Translocating ATPases

Topics

• Adenosine Triphosphate (biosynthesis)
• DNA, Mitochondrial
• Humans
• Kinetics
• Mutation
• Optic Atrophies, Hereditary (genetics)
• Oxidative Phosphorylation
• Proton-Translocating ATPases (genetics, metabolism)
• Syndrome