The NADPH-cytochrome P450 reductase family in Trypanosoma cruzi is involved in the sterol biosynthesis pathway.
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.
De Vas
Matías G
MG
Instituto de Investigaciones en Ingeniería Genética y Biología Molecular (INGEBI) CONICET, Vuelta de Obligado 2490, C1428ADN Buenos Aires, Argentina.
Portal
Patricio
P
Alonso
Guillermo D
GD
Schlesinger
Mariana
M
Flawiá
Mirtha M
MM
Torres
Héctor N
HN
Fernández Villamil
Silvia
S
Paveto
Cristina
C
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*
D013261:Sterols; D009249:NADP; D009251:NADPH-Ferrihemoprotein Reductase