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Arabidopsis thalian...
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Catania, AlessiaCarlo Besta Neurological Institute, IRCCS,University of Paris-Saclay
(author)
Arabidopsis thaliana alternative dehydrogenases : A potential therapy for mitochondrial complex i deficiency? Perspectives and pitfalls
- Article/chapterEnglish2019
Publisher, publication year, extent ...
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2019-10-29
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Springer Science and Business Media LLC,2019
Numbers
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LIBRIS-ID:oai:lup.lub.lu.se:c5a26e8f-0393-49d4-b57f-0df5d4652e6e
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https://lup.lub.lu.se/record/c5a26e8f-0393-49d4-b57f-0df5d4652e6eURI
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https://doi.org/10.1186/s13023-019-1185-3DOI
Supplementary language notes
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Language:English
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Summary in:English
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Subject category:art swepub-publicationtype
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Subject category:ref swepub-contenttype
Notes
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Background: Complex I (CI or NADH:ubiquinone oxidoreductase) deficiency is the most frequent cause of mitochondrial respiratory chain defect. Successful attempts to rescue CI function by introducing an exogenous NADH dehydrogenase, such as the NDI1 from Saccharomyces cerevisiae (ScNDI1), have been reported although with drawbacks related to competition with CI. In contrast to ScNDI1, which is permanently active in yeast naturally devoid of CI, plant alternative NADH dehydrogenases (NDH-2) support the oxidation of NADH only when the CI is metabolically inactive and conceivably when the concentration of matrix NADH exceeds a certain threshold. We therefore explored the feasibility of CI rescue by NDH-2 from Arabidopsis thaliana (At) in human CI defective fibroblasts. Results: We showed that, other than ScNDI1, two different NDH-2 (AtNDA2 and AtNDB4) targeted to the mitochondria were able to rescue CI deficiency and decrease oxidative stress as indicated by a normalization of SOD activity in human CI-defective fibroblasts. We further demonstrated that when expressed in human control fibroblasts, AtNDA2 shows an affinity for NADH oxidation similar to that of CI, thus competing with CI for the oxidation of NADH as opposed to our initial hypothesis. This competition reduced the amount of ATP produced per oxygen atom reduced to water by half in control cells. Conclusions: In conclusion, despite their promising potential to rescue CI defects, due to a possible competition with remaining CI activity, plant NDH-2 should be regarded with caution as potential therapeutic tools for human mitochondrial diseases.
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Iuso, ArcangelaHelmholtz Zentrum München,Technical University of Munich
(author)
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Bouchereau, JulietteHôpital universitaire Robert-Debré,University of Paris-Saclay
(author)
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Kremer, Laura S.Technical University of Munich,Helmholtz Zentrum München
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Paviolo, MarinaHôpital universitaire Robert-Debré,University of Paris-Saclay
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Terrile, CaterinaHelmholtz Zentrum München
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Bénit, PauleUniversity of Paris-Saclay
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Rasmusson, Allan G.Lund University,Lunds universitet,Molekylär cellbiologi,Biologiska institutionen,Naturvetenskapliga fakulteten,Molecular Cell Biology,Department of Biology,Faculty of Science(Swepub:lu)fysb-ara
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Schwarzmayr, ThomasHelmholtz Zentrum München,Ludwig-Maximilian University of Munich
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Tiranti, ValeriaCarlo Besta Neurological Institute, IRCCS
(author)
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Rustin, PierreUniversity of Paris-Saclay
(author)
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Rak, MalgorzataUniversity of Paris-Saclay
(author)
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Prokisch, HolgerTechnical University of Munich,Helmholtz Zentrum München
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Schiff, ManuelUniversity of Paris-Saclay,Hôpital universitaire Robert-Debré
(author)
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Carlo Besta Neurological Institute, IRCCSUniversity of Paris-Saclay
(creator_code:org_t)
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In:Orphanet Journal of Rare Diseases: Springer Science and Business Media LLC14:11750-1172
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Catania, Alessia
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Iuso, Arcangela
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Bouchereau, Juli ...
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Kremer, Laura S.
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Paviolo, Marina
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Terrile, Caterin ...
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Bénit, Paule
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Rasmusson, Allan ...
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Schwarzmayr, Tho ...
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Tiranti, Valeria
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Rustin, Pierre
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Rak, Malgorzata
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Prokisch, Holger
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Schiff, Manuel
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