BACKGROUND: Every eukaryote requires iron, which is also true for the parasitic protist Trypanosoma brucei, the causative agent of sleeping sickness in humans and nagana in cattle. T. brucei undergoes a complex life cycle during which its single mitochondrion is subject to major metabolic and morphological changes. SCOPE OF REVIEW: This review covers what is known about processes associated with iron-sulfur clusters and heme metabolism in T. brucei. We discuss strategies by which iron and heme are acquired and utilized by this model parasite, emphasizing the differences between its two life cycle stages residing in the bloodstream of the mammalian host and gut of the insect vector. Finally, the role of iron in the host-parasite interactions is discussed along with their possible exploitation in fighting these deadly parasites. MAJOR CONCLUSIONS: The processes associated with acquisition and utilization of iron, distinct in the two life stages of T. brucei, are fine tuned for the dramatically different host environment occupied by them. Although the composition and compartmentalization of the iron-sulfur cluster assembly seem to be conserved, some unique features of the iron acquisition strategies may be exploited for medical interventions against these parasites. GENERAL SIGNIFICANCE: As early-branching protists, trypanosomes and related flagellates are known to harbor an array of unique features, with the acquisition of iron being another peculiarity. Thanks to intense research within the last decade, understanding of iron-sulfur cluster assembly and iron metabolism in T. brucei is among the most advanced of all eukaryotes.

Biology Centre Institute of Parasitology Czech Academy of Sciences 37005 České Budějovice Czech Republic

Biology Centre Institute of Parasitology Czech Academy of Sciences 37005 České Budějovice Czech Republic; Canadian Institute for Advanced Research Toronto Canada

Biology Centre Institute of Parasitology Czech Academy of Sciences 37005 České Budějovice Czech Republic; Institut für Zytobiologie Philipps Universität Marburg 35032 Marburg Germany

References provided by Crossref.org

Adaptive iron utilization compensates for the lack of an inducible uptake system in Naegleria fowleri and represents a potential target for therapeutic intervention

Branched late-steps of the cytosolic iron-sulphur cluster assembly machinery of Trypanosoma brucei

Fe-S cluster assembly in the supergroup Excavata

Heme pathway evolution in kinetoplastid protists