title: The adaptative mechanisms of Trypanosoma brucei for sterol homeostasis in its different life-cycle environments.
abstract: Bloodstream forms of Trypanosoma brucei do not synthesize sterols de novo and therefore cannot survive in medium devoid of lipoproteins. Growth of parasites is essentially supported by receptor-mediated endocytosis of low-density lipoproteins (LDLs), which carry phospholipids and cholesteryl esters. These lipids are released from internalized LDL after apoprotein B-100 is degraded by acidic thiol-proteases in the endolysosomal apparatus and then metabolized, as in mammalian cells. The LDL receptor is recycled and its expression is regulated by the sterol stores. Documented pharmacological and immunological interferences with LDL receptor-mediated lipid supply to the bloodstream forms are summarized, and the potential for new approaches to fight against these parasites is evaluated. In contrast to bloodstream forms, cultured procyclic forms can acquire sterols from both exogenous (lipoprotein endocytosis) and endogenous (biosynthesis of ergosterol) sources. The rate-limiting steps of both endocytosis (surface LDL receptor expression) and biosynthesis (3-hydroxy-3-methylglutaryl coenzyme A reductase activity) are regulated by the cellular content of sterol. These two pathways thus complement each other to yield a balanced sterol supply, which demonstrates adaptative capacities to survive in totally different environments and fine regulatory mechanisms of sterol homeostasis.
authors.affiliation: Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520-8022, USA. isabelle.coppens@yale.edu
authors.forename: I
authors.initials: I
authors.lastname: Coppens
authors.forename: P J
authors.initials: PJ
authors.lastname: Courtoy
mesh_terms: D000220:Adaptation, Biological; D000818:Animals; D001692:Biological Transport; D004705:Endocytosis; D006706:Homeostasis; D008077:Lipoproteins, LDL / Q000378:metabolism; D011973:Receptors, LDL / Q000378:metabolism; D013261:Sterols / Q000378:metabolism*; D014346:Trypanosoma brucei brucei / Q000502:physiology*
chemical_list: D008077:Lipoproteins, LDL; D011973:Receptors, LDL; D013261:Sterols