Artículo

Lai, D.-H.; Poropat, E.; Pravia, C.; Landoni, M.; Couto, A.S.; Pérez Rojo, F.G.; Fuchs, A.G.; Dubin, M.; Elingold, I.; Rodríguez, J.B.; Ferella, M.; Esteva, M.I.; Bontempi, E.J.; Lukeš, J. "Solanesyl diphosphate synthase, an enzyme of the ubiquinone synthetic pathway, is required throughout the life cycle of Trypanosoma brucei" (2014) Eukaryotic Cell. 13(2):320-328
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Abstract:

Ubiquinone 9 (UQ9), the expected product of the long-chain solanesyl diphosphate synthase of Trypanosoma brucei (TbSPPS), has a central role in reoxidation of reducing equivalents in the mitochondrion of T. brucei. The ablation of TbSPPS gene expression by RNA interference increased the generation of reactive oxygen species and reduced cell growth and oxygen consumption. The addition of glycerol to the culture medium exacerbated the phenotype by blocking its endogenous generation and excretion. The participation of TbSPPS in UQ synthesis was further confirmed by growth rescue using UQ with 10 isoprenyl subunits (UQ10). Furthermore, the survival of infected mice was prolonged upon the downregulation of TbSPPS and/or the addition of glycerol to drinking water. TbSPPS is inhibited by 1-[(n-oct-1-ylamino)ethyl] 1,1-bisphosphonic acid, and treatment with this compound was lethal for the cells. The findings that both UQ9 and ATP pools were severely depleted by the drug and that exogenous UQ10 was able to fully rescue growth of the inhibited parasites strongly suggest that TbSPPS and UQ synthesis are the main targets of the drug. These two strategies highlight the importance of TbSPPS for T. brucei, justifying further efforts to validate it as a new drug target. © 2014, American Society for Microbiology. All Rights Reserved.

Registro:

Documento: Artículo
Título:Solanesyl diphosphate synthase, an enzyme of the ubiquinone synthetic pathway, is required throughout the life cycle of Trypanosoma brucei
Autor:Lai, D.-H.; Poropat, E.; Pravia, C.; Landoni, M.; Couto, A.S.; Pérez Rojo, F.G.; Fuchs, A.G.; Dubin, M.; Elingold, I.; Rodríguez, J.B.; Ferella, M.; Esteva, M.I.; Bontempi, E.J.; Lukeš, J.
Filiación:Biology Centre, Institute of Parasitology, Academy of Sciences of the Czech Republic, České Budějovice, Czech Republic
University of South Bohemia, České Budějovice, Czech Republic
Instituto Nacional de Parasitología Dr. M. Fatala Chabén, Ministerio de Salud, Buenos Aires, Argentina
CIHIDECAR, Departamento de Química Orgánica, Universidad de Buenos Aires, Buenos Aires, Argentina
CAECIHS, Universidad Abierta Interamericana, Buenos Aires, Argentina
CEFYBO, UBA-CONICET, Buenos Aires, Argentina
Departamento de Química Orgánica and UMYMFOR, Universidad de Buenos Aires, Buenos Aires, Argentina
Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden
Center for Parasitic Organisms, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-Sen University, Guangzhou, China
Palabras clave:(E) N2 carbamoyl N1 ((6 chloro 3 pyridyl)methyl) N1 methylacetamidine; (E)- N2-carbamoyl-N1-((6-chloro-3-pyridyl)methyl)-N1-methylacetamidine; doxycycline; enzyme inhibitor; glycerol; nitrile; octaprenyltransferase; protozoal protein; pyridine derivative; reactive oxygen metabolite; trans-octaprenyltranstransferase; transferase; ubiquinone; animal; article; biosynthesis; drug antagonism; enzymology; genetics; growth, development and aging; life cycle stage; metabolism; mouse; pathogenicity; Trypanosoma brucei; trypanosomiasis; Alkyl and Aryl Transferases; Animals; Doxycycline; Enzyme Inhibitors; Glycerol; Life Cycle Stages; Mice; Nitriles; Protozoan Proteins; Pyridines; Reactive Oxygen Species; Trypanosoma brucei brucei; Trypanosomiasis; Ubiquinone
Año:2014
Volumen:13
Número:2
Página de inicio:320
Página de fin:328
DOI: http://dx.doi.org/10.1128/EC.00271-13
Título revista:Eukaryotic Cell
Título revista abreviado:Eukaryotic Cell
ISSN:15359778
CODEN:ECUEA
CAS:doxycycline, 10592-13-9, 17086-28-1, 564-25-0, 94088-85-4; glycerol, 56-81-5; transferase, 9047-61-4; ubiquinone, 1339-63-5
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_15359778_v13_n2_p320_Lai

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Citas:

---------- APA ----------
Lai, D.-H., Poropat, E., Pravia, C., Landoni, M., Couto, A.S., Pérez Rojo, F.G., Fuchs, A.G.,..., Lukeš, J. (2014) . Solanesyl diphosphate synthase, an enzyme of the ubiquinone synthetic pathway, is required throughout the life cycle of Trypanosoma brucei. Eukaryotic Cell, 13(2), 320-328.
http://dx.doi.org/10.1128/EC.00271-13
---------- CHICAGO ----------
Lai, D.-H., Poropat, E., Pravia, C., Landoni, M., Couto, A.S., Pérez Rojo, F.G., et al. "Solanesyl diphosphate synthase, an enzyme of the ubiquinone synthetic pathway, is required throughout the life cycle of Trypanosoma brucei" . Eukaryotic Cell 13, no. 2 (2014) : 320-328.
http://dx.doi.org/10.1128/EC.00271-13
---------- MLA ----------
Lai, D.-H., Poropat, E., Pravia, C., Landoni, M., Couto, A.S., Pérez Rojo, F.G., et al. "Solanesyl diphosphate synthase, an enzyme of the ubiquinone synthetic pathway, is required throughout the life cycle of Trypanosoma brucei" . Eukaryotic Cell, vol. 13, no. 2, 2014, pp. 320-328.
http://dx.doi.org/10.1128/EC.00271-13
---------- VANCOUVER ----------
Lai, D.-H., Poropat, E., Pravia, C., Landoni, M., Couto, A.S., Pérez Rojo, F.G., et al. Solanesyl diphosphate synthase, an enzyme of the ubiquinone synthetic pathway, is required throughout the life cycle of Trypanosoma brucei. Eukaryotic Cell. 2014;13(2):320-328.
http://dx.doi.org/10.1128/EC.00271-13