Expression of Ndi1p, an alternative NADH:ubiquinone oxidoreductase, increases mitochondrial membrane potential in a C. elegans model of mitochondrial disease.
Biochim Biophys Acta
; 1767(9): 1157-63, 2007 Sep.
Article
en En
| MEDLINE
| ID: mdl-17706937
ABSTRACT
The NADHubiquinone oxidoreductase or complex I of the mitochondrial respiratory chain is an intricate enzyme with a vital role in energy metabolism. Mutations affecting complex I can affect at least three processes; they can impair the oxidation of NADH, reduce the enzyme's ability to pump protons for the generation of a mitochondrial membrane potential and increase the production of damaging reactive oxygen species. We have previously developed a nematode model of complex I-associated mitochondrial dysfunction that features hallmark characteristics of mitochondrial disease, such as lactic acidosis and decreased respiration. We have expressed the Saccharomyces cerevisiae NDI1 gene, which encodes a single subunit NADH dehydrogenase, in a strain of Caenorhabditis elegans with an impaired complex I. Expression of Ndi1p produces marked improvements in animal fitness and reproduction, increases respiration rates and restores mitochondrial membrane potential to wild type levels. Ndi1p functionally integrates into the nematode respiratory chain and mitigates the deleterious effects of a complex I deficit. However, we have also shown that Ndi1p cannot substitute for the absence of complex I. Nevertheless, the yeast Ndi1p should be considered as a candidate for gene therapy in human diseases involving complex I.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Enfermedades Mitocondriales
/
Proteínas de Saccharomyces cerevisiae
/
Potencial de la Membrana Mitocondrial
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NADH Deshidrogenasa
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Biochim Biophys Acta
Año:
2007
Tipo del documento:
Article