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NADH dehydrogenase of Trypanosoma brucei is important for efficient acetate production in bloodstream forms

In the slender bloodstream form, Trypanosoma brucei mitochondria are repressed for many functions. Multiple components of mitochondrial complex I, NADH:ubiquinone oxidoreductase, are expressed in this stage, but electron transfer through complex I is not essential. Here we investigate the role of th...

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Autores principales: Surve, Sachin V., Jensen, Bryan C., Heestand, Meredith, Mazet, Muriel, Smith, Terry K., Bringaud, Frédéric, Parsons, Marilyn, Schnaufer, Achim
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier/North-Holland Biomedical Press 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5225879/
https://www.ncbi.nlm.nih.gov/pubmed/27717801
http://dx.doi.org/10.1016/j.molbiopara.2016.10.001
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author Surve, Sachin V.
Jensen, Bryan C.
Heestand, Meredith
Mazet, Muriel
Smith, Terry K.
Bringaud, Frédéric
Parsons, Marilyn
Schnaufer, Achim
author_facet Surve, Sachin V.
Jensen, Bryan C.
Heestand, Meredith
Mazet, Muriel
Smith, Terry K.
Bringaud, Frédéric
Parsons, Marilyn
Schnaufer, Achim
author_sort Surve, Sachin V.
collection PubMed
description In the slender bloodstream form, Trypanosoma brucei mitochondria are repressed for many functions. Multiple components of mitochondrial complex I, NADH:ubiquinone oxidoreductase, are expressed in this stage, but electron transfer through complex I is not essential. Here we investigate the role of the parasite’s second NADH:ubiquinone oxidoreductase, NDH2, which is composed of a single subunit that also localizes to the mitochondrion. While inducible knockdown of NDH2 had a modest growth effect in bloodstream forms, NDH2 null mutants, as well as inducible knockdowns in a complex I deficient background, showed a greater reduction in growth. Altering the NAD(+)/NADH balance would affect numerous processes directly and indirectly, including acetate production. Indeed, loss of NDH2 led to reduced levels of acetate, which is required for several essential pathways in bloodstream form T. brucei and which may have contributed to the observed growth defect. In conclusion our study shows that NDH2 is important, but not essential, in proliferating bloodstream forms of T. brucei, arguing that the mitochondrial NAD(+)/NADH balance is important in this stage, even though the mitochondrion itself is not actively engaged in the generation of ATP.
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spelling pubmed-52258792017-01-19 NADH dehydrogenase of Trypanosoma brucei is important for efficient acetate production in bloodstream forms Surve, Sachin V. Jensen, Bryan C. Heestand, Meredith Mazet, Muriel Smith, Terry K. Bringaud, Frédéric Parsons, Marilyn Schnaufer, Achim Mol Biochem Parasitol Short Technical Report In the slender bloodstream form, Trypanosoma brucei mitochondria are repressed for many functions. Multiple components of mitochondrial complex I, NADH:ubiquinone oxidoreductase, are expressed in this stage, but electron transfer through complex I is not essential. Here we investigate the role of the parasite’s second NADH:ubiquinone oxidoreductase, NDH2, which is composed of a single subunit that also localizes to the mitochondrion. While inducible knockdown of NDH2 had a modest growth effect in bloodstream forms, NDH2 null mutants, as well as inducible knockdowns in a complex I deficient background, showed a greater reduction in growth. Altering the NAD(+)/NADH balance would affect numerous processes directly and indirectly, including acetate production. Indeed, loss of NDH2 led to reduced levels of acetate, which is required for several essential pathways in bloodstream form T. brucei and which may have contributed to the observed growth defect. In conclusion our study shows that NDH2 is important, but not essential, in proliferating bloodstream forms of T. brucei, arguing that the mitochondrial NAD(+)/NADH balance is important in this stage, even though the mitochondrion itself is not actively engaged in the generation of ATP. Elsevier/North-Holland Biomedical Press 2017-01 /pmc/articles/PMC5225879/ /pubmed/27717801 http://dx.doi.org/10.1016/j.molbiopara.2016.10.001 Text en © 2016 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Short Technical Report
Surve, Sachin V.
Jensen, Bryan C.
Heestand, Meredith
Mazet, Muriel
Smith, Terry K.
Bringaud, Frédéric
Parsons, Marilyn
Schnaufer, Achim
NADH dehydrogenase of Trypanosoma brucei is important for efficient acetate production in bloodstream forms
title NADH dehydrogenase of Trypanosoma brucei is important for efficient acetate production in bloodstream forms
title_full NADH dehydrogenase of Trypanosoma brucei is important for efficient acetate production in bloodstream forms
title_fullStr NADH dehydrogenase of Trypanosoma brucei is important for efficient acetate production in bloodstream forms
title_full_unstemmed NADH dehydrogenase of Trypanosoma brucei is important for efficient acetate production in bloodstream forms
title_short NADH dehydrogenase of Trypanosoma brucei is important for efficient acetate production in bloodstream forms
title_sort nadh dehydrogenase of trypanosoma brucei is important for efficient acetate production in bloodstream forms
topic Short Technical Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5225879/
https://www.ncbi.nlm.nih.gov/pubmed/27717801
http://dx.doi.org/10.1016/j.molbiopara.2016.10.001
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