Discussion

Trypanosoma brucei is a lethal human parasite with a complex life cycle that alternates between a mammalian host and the blood-feeding insect vector, a tsetse fly. Exposed to vastly different nutritional environments throughout their distinct life stages, they must adapt their energy metabolism accordingly. With access to abundant glucose, the intercellular bloodstream stage is able to produce sufficient ATP by aerobic glycolysis, while the insect stage depends on amino acid catabolism and mitochondrial oxidative phosphorylation for efficient ATP synthesis. Therefore, during the complex development of the parasite in the tsetse fly, the single mitochondrion undergoes dramatic structural and metabolic changes. Until recently, it was challenging to work with the various intermediate life stages, but now each of the insect vector developmental cell types can be created in vitro by simply overexpressing a single RNA binding protein. Our preliminary data with this cell line suggests that the molecular mechanisms responsible for the metabolic rewiring may be similar to what is described in cancer cells. We observe increased expression of TbIF1, the T. brucei inhibitory factor of the FoF1-ATPase, and the subsequent increase in ROS production that potentially signals a switch to aerobic glycolysis. The putative role of TbIF1 in mitochondrial remodeling during T. brucei differentiation will be discussed.