Host plasma low density lipoprotein particles as an essential source of lipids for the bloodstream forms of Trypanosoma brucei.
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 [3H]sphingomyelin and of LDL-associated [3H]cholesteryl oleate paralleled each other, and that of 125I-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.
Coppens
I
I
Cell Biology Unit, University of Louvain Medical School, Brussels, Belgium.
Levade
T
T
Courtoy
P J
PJ
D000818:Animals; D001692:Biological Transport; D002788:Cholesterol Esters / Q000378:metabolism; D008078:Cholesterol, LDL / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008049:Lipase / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000097:blood* / Q000302:isolation & purification; D010713:Phosphatidylcholines / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013109:Sphingomyelins / Q000378:metabolism; D013997:Time Factors; D014280:Triglycerides / Q000378:metabolism; D014316:Tritium; D014346:Trypanosoma brucei brucei / Q000378:metabolism*
D002788:Cholesterol Esters; D008078:Cholesterol, LDL; D008077:Lipoproteins, LDL; D010713:Phosphatidylcholines; D013109:Sphingomyelins; D014280:Triglycerides; D014316:Tritium; C014409:cholesteryl oleate; D008049:Lipase