Mitochondrial Protein Biogenesis in African Trypanosomes
Trypanosomatid parasites of the genera Leishmania and Trypanosoma, infect millions of people worldwide. This group of early branching eukaryotes possesses single reticular mitochondrion per cell with a concatenated structure of mitochondrial DNA known as kinetoplast or kDNA. Besides, parasite mitochondrion possesses several other novel features, thus represents a useful source of potential chemotherapeutic target. Similar to other eukaryotes, trypanosomatids also import hundreds of proteins into mitochondria for their function. However, mitochondrial protein import machinery has been least characterized in this group of organisms. As part of this machinery, we characterized several parasite-specific proteins of Trypanosoma brucei mitochondrion. We discovered that T. brucei possesses an evolutionarily divergent and modular type protein translocase of the mitochondrial inner membrane (TIM). The goal of our project is to define the structure of this essential protein complex in T. brucei, to determine its mechanism of action, and to identify novel protein-protein interaction domains critical for the survival of this parasite. Later this knowledge can be utilized to design novel therapy for these diseases. These studies will also provide functional and evolutionary insights into mitochondrial protein import machinery and mechanisms in eukaryotes.
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