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MtDNA mutations associated with Leber's hereditary optic neuropathy: studies on cytoplasmic hybrid (cybrid) cells.

Abstract：

:Leber's hereditary optic neuropathy (LHON) has been associated with "primary" and "secondary" mtDNA missense point mutations, and a synergistic role has been proposed for secondary mutations. No previous study has investigated the effects of LHON primary or primary plus secondary mutations on the respiratory competence of cell lines. We constructed and compared cybrid cell lines obtained from two unrelated LHON patients both carrying the common 11778/ND4 primary mutation. One of the patients also carried the 13708/ND5 and 4216/ND1 secondary mutations. The cybrid clones were evaluated for growth efficiency, oxygen consumption, complexes I, III and IV enzymatic activity and mitochondrial protein synthesis. Complex activity and mitochondrial protein synthesis were not significantly changed in cybrid clones from the patients. Oxygen consumption was significantly decreased in all clones carrying the 11778/ND4 primary mutation demonstrating its pathogenic role in impairing cell respiration. Clones also carrying the secondary mutations showed an even lower oxygen consumption and a significantly higher doubling time, suggesting that the co-presence of the secondary mutations could be relevant in further reducing the cell fitness.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Vergani L,Martinuzzi A,Carelli V,Cortelli P,Montagna P,Schievano G,Carrozzo R,Angelini C,Lugaresi E

doi

10.1006/bbrc.1995.1740

subject

Has Abstract

pub_date

1995-05-25 00:00:00

pages

880-8

issue

3

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(85)71740-8

journal_volume

210

pub_type

杂志文章

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