The objective of this research is to analyze the developmental regulation of mitochondrial ATP synthase biosynthesis and function in the parasitic protozoan Trypanosoma brucei during its differentiation from mammalian to insect (tsetse fly) host specificity. This differention is accompanied by mitochondrial biogenesis, derepression of the mitochondrial genome, and a swith from glycolytic to respiratory energy metabolism; and is advocated as a model system for mitochondrial biogenesis in eukaryotes. The subunit structure of the enzyme, and its regulation by inhibitor or activator proteins, will be examined in different developmental forms of the trypanosome. These experiments will be accompanied by cloning and structural analysis of enzyme genes and gene transcripts, and a test of the possibility that editing of these transcripts occurs in some developmental stages. It is intended that the combined result of these studies will reveal the molecular basis and regulatory mechanism of the developmental shift in ATP synthase activity that occurs in this system. In addition, this research has potential to contribute generally to knowledge of regulation of polysubunit enzymes in differentiating systems.
