Abstract
One striking feature of the biology of trypanosomes is the changes in mitochondrial structure and function that occur as these parasites transition from one life cycle stage to another. Our laboratory has been interested in the role the mitochondrial ATP synthase plays in mitochondrial changes through the life cycle. Analysis of the recently completed T. brucei genome suggested that there may be multiple putative genes encoding ATP synthase subunit c. While homologous in their 3′ ends, these genes differ in their 5′ ends and, if expressed, would result in three distinct proteins. Our analysis showed that all three of the possible transcripts were detected in both procyclic and bloodstream stages, although the c-3 transcript was less abundant than that for c-1 or c-2. The three isoforms of subunit c are produced in both the bloodstream and procyclic stages and their mature protein products possess distinct N-terminal regions of the protein as found within mitochondria. All three isoforms are also incorporated into the assembled ATP synthase complex from procyclic cells. Although multiple subunit c genes have been found in other organisms, they produce identical polypeptides and the finding of significant differences in the mature proteins is unique to T. brucei.
Highlights
Stage coordinated biochemical changes occur throughout the life cycle of Trypanosoma brucei allowing the parasite to maximize carbon source usage depending on the environment [1,2]
Three Potential Subunit C Genes are Present in the Trypanosoma brucei Genome
Previous work from this laboratory identified a single gene for the ATP synthase subunit c (designated c-1 in Figure 1, accession number AAC48310 (Tb11.02.2950), named S9 in previous publications [29])
Summary
Stage coordinated biochemical changes occur throughout the life cycle of Trypanosoma brucei allowing the parasite to maximize carbon source usage depending on the environment [1,2]. This occurs together with vast changes in mitochondrial morphology and protein expression. The functions of oxidative phosphorylation are not initiated until passage into the insect vector and subsequent development of the procyclic form [2] Despite these changes in the mitochondria, the ATP synthase is present in all life cycle stages of T. brucei [3]. Functional assays and protein analysis have shown that the ATP synthase is moderately developmentally regulated throughout the life cycle of the parasite [4] with the highest levels present in the procyclic stage
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