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Arabidopsis thalian...
Arabidopsis thaliana alternative dehydrogenases : A potential therapy for mitochondrial complex i deficiency? Perspectives and pitfalls
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- Catania, Alessia (författare)
- Carlo Besta Neurological Institute, IRCCS,University of Paris-Saclay
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- Iuso, Arcangela (författare)
- Helmholtz Zentrum München,Technical University of Munich
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- Bouchereau, Juliette (författare)
- Hôpital universitaire Robert-Debré,University of Paris-Saclay
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- Kremer, Laura S. (författare)
- Technical University of Munich,Helmholtz Zentrum München
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- Paviolo, Marina (författare)
- Hôpital universitaire Robert-Debré,University of Paris-Saclay
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- Terrile, Caterina (författare)
- Helmholtz Zentrum München
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- Bénit, Paule (författare)
- University of Paris-Saclay
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- Rasmusson, Allan G. (författare)
- Lund University,Lunds universitet,Molekylär cellbiologi,Biologiska institutionen,Naturvetenskapliga fakulteten,Molecular Cell Biology,Department of Biology,Faculty of Science
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- Schwarzmayr, Thomas (författare)
- Helmholtz Zentrum München,Ludwig-Maximilian University of Munich
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- Tiranti, Valeria (författare)
- Carlo Besta Neurological Institute, IRCCS
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- Rustin, Pierre (författare)
- University of Paris-Saclay
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- Rak, Malgorzata (författare)
- University of Paris-Saclay
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- Prokisch, Holger (författare)
- Technical University of Munich,Helmholtz Zentrum München
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- Schiff, Manuel (författare)
- University of Paris-Saclay,Hôpital universitaire Robert-Debré
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(creator_code:org_t)
- 2019-10-29
- 2019
- Engelska.
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Ingår i: Orphanet Journal of Rare Diseases. - : Springer Science and Business Media LLC. - 1750-1172. ; 14:1
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http://dx.doi.org/10... (free)
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https://ojrd.biomedc...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- 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.
Ämnesord
- NATURVETENSKAP -- Biologi -- Cellbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Cell Biology (hsv//eng)
Nyckelord
- Alternative dehydrogenases
- Arabidopsis thaliana
- AtNDA2
- Complex I
- Mitochondria
- Mitochondrial diseases
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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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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visa fler...
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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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visa färre...
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- NATURVETENSKAP
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NATURVETENSKAP
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och Biologi
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och Cellbiologi
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Orphanet Journal ...
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Lunds universitet