The NADPH-cytochrome P450 reductase family in Trypanosoma cruzi is involved in the sterol biosynthesis pathway

DE VAS MATIAS; PORTAL PATRICIO; ALONSO GUILLERMO; SCHLESINGER MARIANA; FLAWIÁ MIRTHA; TORRES HÉCTOR; FERNANDEZ VILLAMIL SILVIA; PAVETO CRISTINA

INTERNATIONAL JOURNAL FOR PARASITOLOGY

ELSEVIER SCI LTD

Año: 2011 vol. 41 p. 99 - 108

0020-7519

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.