Intrinsic uncoupling of cytochrome c oxidase may cause the maternally inherited mitochondrial diseases MELAS and LHON

FEBS Letters

Mather, Michael W¹  Rottenberg, Hagai¹ 

[1] Department of Pathology and Laboratory Medicine, MCP/Hahnemann School of Medicine, Allegheny University of the Health Sciences, M.S. 435, Broad and Vine Streets, Philadelphia, PA 19102, USA

关键词: Mitochondrial disease;    Cytochrome c oxidase;    Proton pumping;    Membrane potential;    Paracoccus denitrificans;    CO;    cytochrome c oxidase;    HEPES;    N-2-hydroxyethylpiperazine-N′-2-ethanesulfonic acid;    LHON;    Leber's hereditary optic neuropathy;    MELAS;    myoclonic encephalomyopathy with lactic acidosis and stroke-like episodes;    mt;    mitochondrial;    PDB;    Protein Data Base;    TM;    transmembrane helix (of a polypeptide);    TMPD;    N;    N;    N′;    N′-tetramethyl-p-phenylenediamine;    TPP+;    tetraphenyl phosphonium ion;    wt;    wild type;   

DOI  :  10.1016/S0014-5793(98)00891-6

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Mutations in the human mtDNA gene encoding subunit III of cytochrome c oxidase (CO) have been reported to cause MELAS and LHON. Paracoccus denitrificans cells expressing substitutions homologous to these MELAS- and LHON-causing mutations had lower growth yield than wild type cells and lower efficiency of proton pumping by CO (e.g. lower H⁺/e⁻ ratio and lower ΔΨ), but had similar CO activity. These results indicate that both substitutions (F263L>A212T) cause intrinsic uncoupling, which may be the direct cause of the diseases. These results also suggest that subunit III is involved in proton pumping.

【 授权许可】

Unknown