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Mutations in subunit 6 of the F 1 F 0 ‐ATP synthase cause two entirely different diseases
Author(s) -
Majander Anna,
Lamminen Tarja,
Juvonen Vesa,
Aula Pertti,
Nikoskelainen Eeva,
Savontaus Marja-Liisa,
Wikström Mårten
Publication year - 1997
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(97)00757-6
Subject(s) - atp synthase , mutant , protein subunit , mutation , mitochondrion , oxidative phosphorylation , respiratory chain , biology , mitochondrial dna , microbiology and biotechnology , gene , genetics , biochemistry
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 F 0 segment of the F 1 F 0 ‐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 F 0 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.