Trypanosoma brucei Tim50 Plays Critical role in Parasite survival in mammalian hosts

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Trypanosoma brucei, the infectious agent for African trypanosomiasis, undergoes various developmental processes during its digenetic life cyclethat includes a major alteration in mitochondrial activities. It is known that changes in mitochondrial functions is critical for the parasite to adapt in different environmental conditions, however, the communication mechanism between this single organelle with the rest of the cell is not clear in T. brucei. Mitochondrial inner membrane protein translocase, TbTim50, have a pair of characteristic DXDX(T/V) phosphatase signature motifs. Here we showed that the recombinant TbTim50, specifically binds with Phosphatidic acid (PA). We have also demonstrated that, TbTim50 possesses a protein phosphatase activity and also able to hydrolyze phosphatidic acid (PA). This is suggesting that TbTim50 likely possesses both protein and lipid phosphatase activities. TbTim50 knockdown (KD) decreased the levels of cardiolipin in comparison to control. Cardiolipin is known to play important roles in various mitochondrial functions. RT-PCR analysis also showed that TbTim50 KD increased expression of multiple genes specific for the stumpy form, a non-dividing differentiated bloodstream form of T. brucei. Importantly, we observed that TbTim50 depleted parasites were unable to establish infection in mice and rats. These results indicates that TbTim50 is essential for overall mitochondrial functions and play a critical role in parasite infectivity in animals.