Mitochondrial energy metabolism and its developmental regulation in Trypanosoma

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Our view of the relatedness and evolution of energy producing endosymbiont-derived organelles like mitochondria and hydrogenosomes has been much shaped by the comparison of their metabolism. Trypanosomes represent an early branch of eukaryotic evolution and our recent work shows that their energy metabolism is, in contrast to common belief, much different from higher eukaryotes. Among other features, their mitochondria share with hydrogenosomes the enzyme acetyl succinyl CoA transferase (ASCT) and use it for acetate secretion. We have cloned the first ASCT gene and take advantage of the excellent reverse genetic tools in the T. brucei system to investigate the metabolism upon genetic manipulations of ASCT expression. Trypanosomes with targeted deletion of the citric acid cycle enzyme aconitase are perfectly heathy in the tsetse fly midgut but show a dramatic developmental phenotype upon further progression towards salivary gland forms. We will test the hypothesis that mitochondrial energy metabolism is radically remodeled by the arthropod host environment that harbours the trypanosomes. Comparison of the metabolism of trypanosomatid mitochondria to other protists and investigation of the adaptability and host control of this metabolism are both expected to shed some light on the properties of early endosymbiont derivatives.