title: The NADPH-cytochrome P450 reductase family in Trypanosoma cruzi is involved in the sterol biosynthesis pathway.
abstract: Trypanosoma cruzi flavoproteins TcCPR-A, TcCPR-B and TcCPR-C are members of the NADPH-dependent cytochrome P-450 reductase family expressed in the parasite. Epimastigotes over-expressing TcCPR-B and TcCPR-C showed enhanced ergosterol biosynthesis and increased NADP(+)/NADPH ratio. Transgenic parasites with augmented ergosterol content presented a higher membrane order with a corresponding diminished bulk-phase endocytosis. These results support a significant role for TcCPR-B and TcCPR-C in the sterol biosynthetic pathway and to our knowledge for the first time reveals the participation of more than one CPR in this metabolic route. Notably, TcCPR-B was found in reservosomes while TcCPR-C localised in the endoplasmic reticulum. In addition, we suggest a different role for TcCPR-A, since its over-expression is lethal, displaying cells with an increased DNA content, aberrant morphology and severe ultrastructural alterations.
authors.affiliation: Instituto de Investigaciones en Ingeniería Genética y Biología Molecular (INGEBI) CONICET, Vuelta de Obligado 2490, C1428ADN Buenos Aires, Argentina.
authors.forename: Matías G
authors.initials: MG
authors.lastname: De Vas
authors.forename: Patricio
authors.initials: P
authors.lastname: Portal
authors.forename: Guillermo D
authors.initials: GD
authors.lastname: Alonso
authors.forename: Mariana
authors.initials: M
authors.lastname: Schlesinger
authors.forename: Mirtha M
authors.initials: MM
authors.lastname: Flawiá
authors.forename: Héctor N
authors.initials: HN
authors.lastname: Torres
authors.forename: Silvia
authors.initials: S
authors.lastname: Fernández Villamil
authors.forename: Cristina
authors.initials: C
authors.lastname: Paveto
mesh_terms: D000818:Animals; D053898:Biosynthetic Pathways / Q000235:genetics*; D002462:Cell Membrane / Q000737:chemistry; D015870:Gene Expression; D009249:NADP / Q000032:analysis; D009251:NADPH-Ferrihemoprotein Reductase / Q000235:genetics / Q000378:metabolism*; D015388:Organelles / Q000201:enzymology; D010587:Phagocytosis; D013261:Sterols / Q000096:biosynthesis*; D014349:Trypanosoma cruzi / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*
chemical_list: D013261:Sterols; D009249:NADP; D009251:NADPH-Ferrihemoprotein Reductase