MUTATIONS IN SUBUNIT-6 OF THE F1F0-ATP SYNTHASE CAUSE 2 ENTIRELY DIFFERENT DISEASES

A lowered efficiency of oxidative phosphorylation was recently found i n a Leber hereditary optic neuropathy (LHON) proband carrying a mutati on in the mtDNA gene for subunit 6 of the membrane-bound F-0 segment o f the F1F0-ATP synthase [9], This phenotype was transferred to cytopla smic hybrid cells together with the mutation, proving its functional s ignificance, Increasing the respiratory rate in the mitochondria from this mutant raised the ATP/2e(-) ratio back to normal values, A differ ent mutation in the same mtDNA gene has been found in patients with th e NARP syndrome [10], Although the ATP/2e(-) ratio is also decreased i n this mutant, in this case an increase in the respiratory rate could not compensate for it, Whilst both mutations affect submit 6 of the pr oton-translocating F-0 segment, the LHON mutation induces a proton lea k whereas the NARP mutation blocks proton translocation, Hence, the la tter will have much more destructive metabolic consequences in agreeme nt with the large clinical differences between the two diseases. (C) 1 997 Federation of European Biochemical Societies.