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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...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier/North-Holland Biomedical Press
2017
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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. |
format | Online Article Text |
id | pubmed-5225879 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Elsevier/North-Holland Biomedical Press |
record_format | MEDLINE/PubMed |
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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