Files and links (1)
Bhaduri-McIntosh_Sumita_19964.46 MB
PDF Restricted Access, VIEWABLE UPON REQUEST: contact archives@drexel.edu
Dissertation
Molecular aspects of a phosphate carrier of Plasmodium falciparum
Doctor of Philosophy (Ph.D.), Allegheny University of the Health Sciences
Dec 1996
DOI:
https://doi.org/10.17918/00010157
Abstract
Glycolysis is the primary source of energy in erythrocytic stages of malarial parasites and mitochondrial contribution to the ATP pool via oxidative phosphorylation is believed to be absent. While there is no direct evidence for mitochondrial ATP synthesis yet, some of the recent studies seem to indicate its existence. Several components are necessary for mitochondrial oxidative phosphorylation. We have isolated the gene for one such component, a nuclear gene encoding the Plasmodium falciparum homologue of the mitochondrial phosphate carrier (PfMPC). The encoded protein is a member of the family of mitochondrial anion transport proteins which includes proteins such as the adenine nucleotide carrier (ADP/ATP carrier), the uncoupling protein, and the oxoglutarate carrier. Sequence analysis of PfMPC revealed it to be an integral membrane protein with six transmembrane domains, and with significant homology to MPC from other organisms. A 2 kb RNA was detected by Northen blot analysis at similar levels in both asexual and sexual stages, suggesting the presence of PfMPC in both these stages. These results indicate that malarial parasites possess a critical component required for oxidative phosphorylation, and that this component is expressed in asexual stages. Furthermore, analysis of asexual stage-specific PfMPC transcript indicated that its levels are regulated such that it is at a minimum in ring stages and gradually builds up to a peak in late trophozoites. These observations parallel the expected increase in demand for energy within the parasites in late trophozoites. Import studies of PfMPC protein into heterologous mitochondria demonstrated its ability to be imported into mitochondria and thus provided indirect evidence for its mitochondrial location. Direct evidence in the form of antibody studies and functional studies in malarial parasite is lacking. In the absence of evidence to the contrary, other location and hence other unknown functions of PfMPC cannot be ruled out. Information regarding PfMPC transcription are consistent with the suggestion that erythrocytic stages of malarial parasites may possess a potential for mitochondrial ATP synthesis. Although not a primary source, mitochondria in malarial parasites may serve as a secondary source of energy.
Metrics
16 Record Views
Details
- Title
- Molecular aspects of a phosphate carrier of Plasmodium falciparum
- Creators
- Sumita Bhaduri-McIntosh
- Contributors
- James E. Sylvester (Advisor) - Drexel University, Allegheny University of the Health Sciences (1996-1998)
- Awarding Institution
- Allegheny University of the Health Sciences
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Allegheny University of the Health Sciences; Philadelphia, Pennsylvania
- Number of pages
- ix, 111 pages
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- Microbiology and Immunology [Historical]; Allegheny University of the Health Sciences (1996-1998); School of Medicine (1996-1998)
- Other Identifier
- 991021888829604721