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

FEBS Letters

Nikoskelainen, Eeva³  Lamminen, Tarja²  Aula, Pertti²  Juvonen, Vesa²  Majander, Anna¹  Wikström, Mårten¹  Savontaus, Marja-Liisa² 

[1] Helsinki Bioenergetics Group, Department of Medical Chemistry, Institute of Biomedical Sciences and Biocentrum Helsinki. P.O. Box 8, University of Helsinki, FIN-00014 Helsinki, Finland;Department of Medical Genetics, Institute of Biomedicine, University of Turku, FIN-20520 Turku, Finland;Department of Ophthalmology, Turku University Central Hospital, FIN-20520 Turku, Finland

关键词: F0;    Leber's disease;    Leber hereditary optic neuropathy;    Mitochondrial disease;    NARP syndrome;    Proton translocation;   

DOI  :  10.1016/S0014-5793(97)00757-6

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown