title: NADH dehydrogenase of Trypanosoma brucei is important for efficient acetate production in bloodstream forms.
abstract: 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.
authors.affiliation: Center for Infectious Disease Research (Formerly Seattle Biomedical Research Institute), 307 Westlake Ave. N., Seattle, WA, 98109, USA.
authors.forename: Sachin V
authors.initials: SV
authors.lastname: Surve
authors.affiliation: Center for Infectious Disease Research (Formerly Seattle Biomedical Research Institute), 307 Westlake Ave. N., Seattle, WA, 98109, USA.
authors.forename: Bryan C
authors.initials: BC
authors.lastname: Jensen
authors.affiliation: Center for Infectious Disease Research (Formerly Seattle Biomedical Research Institute), 307 Westlake Ave. N., Seattle, WA, 98109, USA.
authors.forename: Meredith
authors.initials: M
authors.lastname: Heestand
authors.affiliation: Centre de Résonance Magnétique des Systèmes Biologiques (RMSB), UMR5536, Université de Bordeaux, CNRS, Bordeaux, France.
authors.forename: Muriel
authors.initials: M
authors.lastname: Mazet
authors.affiliation: Biomedical Sciences Research Complex, University of St Andrews, North Haugh, St. Andrews KY16 9ST, United Kingdom.
authors.forename: Terry K
authors.initials: TK
authors.lastname: Smith
authors.affiliation: Centre de Résonance Magnétique des Systèmes Biologiques (RMSB), UMR5536, Université de Bordeaux, CNRS, Bordeaux, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Bringaud
authors.affiliation: Center for Infectious Disease Research (Formerly Seattle Biomedical Research Institute), 307 Westlake Ave. N., Seattle, WA, 98109, USA; Dept. of Global Health, University of Washington, Seattle, WA, 98195, USA. Electronic address: marilyn.parsons@cidresearch.org.
authors.forename: Marilyn
authors.initials: M
authors.lastname: Parsons
authors.affiliation: Institute of Immunology & Infection Research and Centre of Immunity, Infection & Evolution, The University of Edinburgh, Edinburgh, EH9 3FL, United Kingdom. Electronic address: achim.schnaufer@ed.ac.uk.
authors.forename: Achim
authors.initials: A
authors.lastname: Schnaufer
mesh_terms: D000085:Acetates / Q000378:metabolism*; D042967:Electron Transport Complex I / Q000737:chemistry / Q000378:metabolism; D008018:Life Cycle Stages; D008928:Mitochondria / Q000378:metabolism; D009154:Mutation; D009245:NADH Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport; D014346:Trypanosoma brucei brucei / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism*
chemical_list: D000085:Acetates; D021122:Protein Subunits; D009245:NADH Dehydrogenase; D042967:Electron Transport Complex I
keywords: Acetate; Mitochondrion; NADH:ubiquinone oxidoreductase; NDH2; Respiratory complex I; Trypanosoma brucei