Pyruvate is a key product of glycolysis that regulates the energy metabolism of cells. InTrypanosoma brucei, the causative agent of sleeping sickness, the fate of pyruvate varies dramatically during the parasite life cycle. In bloodstream forms, pyruvate is mainly excreted, whereas in tsetse fly forms, pyruvate is metabolized in mitochondria yielding additional ATP molecules. The character of the molecular machinery that mediates pyruvate transport across mitochondrial membrane was elusive until the recent discovery of mitochondrial pyruvate carrier (MPC) in yeast and mammals. Here, we characterized pyruvate import into mitochondrion ofT. brucei. We identifiedmpc1andmpc2homologs in theT. bruceigenome with attributes of MPC protein family and we demonstrated that both proteins are present in the mitochondrial membrane of the parasite. Investigations ofmpc1ormpc2gene knock-out cells proved thatT. bruceiMPC1/2 proteins facilitate mitochondrial pyruvate transport. Interestingly, MPC is expressed not only in procyclic trypanosomes with fully activated mitochondria but also in bloodstream trypanosomes in which most of pyruvate is excreted. Moreover, MPC appears to be essential for bloodstream forms, supporting the recently emerging picture that the functions of mitochondria in bloodstream forms are more diverse than it was originally thought.
In the course of the complex life cycle of Trypanosoma brucei, dramatic changes to the cellular metabolism occur. While in the bloodstream form pyruvate is mainly excreted, in the procyclic midgut stages transmitted by tsetse it is further oxidized in the mitochondria. Here, we investigate the import of pyruvate into the mitochondrion of T. brucei and report that, surprisingly, mitochondrial pyruvate carrier seems to play an important role in the bloodstream form of the parasite.