In contrast to mammalian cells, bloodstream forms of Trypanosoma brucei show no activity for fatty acid and sterol synthesis and critically depend on plasma low density lipoprotein (LDL) particles for their rapid growth. We report here that these parasites acquire such lipids by receptor-mediated endocytosis of LDL, subsequent lysosomal degradation of apoprotein B-LDL, and utilization of these lipids. Uptake of LDL-associated [H]sphingomyelin and of LDL-associated [H]cholesteryl oleate paralleled each other, and that of I-apoprotein B-LDL showed saturation and could be inhibited by unlabeled LDL or by anti-LDL receptor antibodies. Metabolism of lipids carried by LDL was abolished by chloroquine and by the thiol protease inhibitor, leupeptin. Sphingomyelin was cleaved by an acid sphingomyelinase to yield ceramide, which was itself split up into sphingosine and fatty acids. The latter were further incorporated into phosphatidylcholine, triacylglycerols, or cholesteryl esters. Similarly, cholesteryl oleate was hydrolyzed by an acid lipase to yield free cholesterol, which was reesterified with fatty acids, presumably in the cytosol. Like free cholesterol, LDL provided substrate for cholesterol esterification. In the culture-adapted procyclic form of T. brucei, which is capable of sterol synthesis, exogenous LDL-cholesterol rather than endogenously synthesized sterol was utilized for sterol esterification. Interference with exogenous supply of lipids via receptor-mediated endocytosis of LDL should be explored to fight against trypanosomiasis.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				I. Coppens and K. A. Joiner Host but Not Parasite Cholesterol Controls Toxoplasma Cell Entry by Modulating Organelle Discharge Mol. Biol. Cell, September 1, 2003; 14(9): 3804 - 3820. [Abstract] [Full Text] [PDF]

				H. P. Green, M. del Pilar Molina Portela, E. N. St. Jean, E. B. Lugli, and J. Raper Evidence for a Trypanosoma brucei Lipoprotein Scavenger Receptor J. Biol. Chem., January 3, 2003; 278(1): 422 - 427. [Abstract] [Full Text] [PDF]

				I. Coppens, A. P. Sinai, and K. A. Joiner Toxoplasma gondii Exploits Host Low-Density Lipoprotein Receptor-mediated Endocytosis for Cholesterol Acquisition J. Cell Biol., April 3, 2000; 149(1): 167 - 180. [Abstract] [Full Text] [PDF]

				C. O. Rodrigues, D. A. Scott, and R. Docampo Characterization of a Vacuolar Pyrophosphatase in Trypanosoma brucei and Its Localization to Acidocalcisomes Mol. Cell. Biol., November 1, 1999; 19(11): 7712 - 7723. [Abstract] [Full Text] [PDF]