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The effect of mpc1/mpc2 overexpression in intraerythrocytic Plasmodium falciparum parasites
Dissertation (MSc (Biochemistry))--University of Pretoria, 2024.
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| Format: | Thesis |
| Language: | English |
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University of Pretoria
2025
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| _version_ | 1867613517717176320 |
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| access_status_str | Open Access |
| author2 | Niemand, Jandeli |
| author_browse | Niemand, Jandeli |
| author_facet | Niemand, Jandeli |
| collection | Thesis |
| dc_rights_str_mv | © 2023 University of Pretoria. All rights reserved. The copyright in this work vests in the University of Pretoria. No part of this work may be reproduced or transmitted in any form or by any means, without the prior written permission of the University of Pretoria. |
| description | Dissertation (MSc (Biochemistry))--University of Pretoria, 2024. |
| format | Thesis |
| id | oai:repository.up.ac.za:2263/100949 |
| institution | University of Pretoria (South Africa) |
| language | English |
| last_indexed | 2026-06-10T12:37:24.815Z |
| license_str | Other — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from UPSpace — University of Pretoria Institutional Repository |
| publishDate | 2025 |
| publishDateRange | 2025 |
| publishDateSort | 2025 |
| publisher | University of Pretoria |
| publisherStr | University of Pretoria |
| record_format | dspace |
| source_str | UPSpace — University of Pretoria Institutional Repository |
| spelling | oai:repository.up.ac.za:2263/100949 The effect of mpc1/mpc2 overexpression in intraerythrocytic Plasmodium falciparum parasites Niemand, Jandeli u18001964@tuks.co.za Birkholtz, Lyn-Marie Voges, Suzelle UCTD Sustainable Development Goals (SDGs) Plasmodium falciparum Metabolism Overexpression Mitochondrial pyruvate carrier heterocomplex (MPC) Transgenic Dissertation (MSc (Biochemistry))--University of Pretoria, 2024. Pyruvate functions as a metabolic switch between aerobic and anaerobic metabolism, allowing a shift to an alternate metabolic pathway when required. The mitochondrial pyruvate carrier heterocomplex (MPC), composed of MPC1 and MPC2, has been identified as the transport complex responsible for pyruvate transport into the mitochondria. In P. falciparum, the putatively annotated mpc1 (pf3d7_1340800) and mpc2 (pf3d7_1470400) genes have yet to be characterised. In this study, the mpc1 and mpc2 genes in P. falciparum parasites were investigated using an overexpression approach. A transgenic P. falciparum parasite line constitutively expressing mpc1/mpc2 above basal level was established, and increased MPC abundance was confirmed. The transgenic parasites were then compared to the wild-type to confirm that the genetic modification allowing the mpc1/mpc2 overexpression did not negatively affect intraerythrocytic parasite proliferation, survival, or morphology. Likewise, mitochondrial viability, abundance of other mitochondrial metabolism proteins, and parasite sensitivity to compounds inhibiting mitochondrial function was also unaffected. To gain insight into the biology surrounding the activity of the mpc1/mpc2 genes, the downstream effects of mpc1/mpc2 overexpression in the transgenic and wild-type P. falciparum parasites lines were compared. Chemical interrogation with an MPC inhibitor indicated a reduction in parasite sensitivity to the inhibitor upon mpc1/mpc2 overexpression, whereas no difference in the parasite sensitivity was observed when treated with other types of inhibitors. The overexpression of mpc1/mpc2 resulted in reduced lactate production, as expected, since less pyruvate would remain in the cytosol to be converted into lactate. Additionally, mpc1/mpc2 overexpression promoted parasite survival during glutamine starvation as expected, since more pyruvate can enter the mitochondria to drive the TCA cycle to compensate for the lack of glutamine. Therefore, increased mpc1/mpc2 expression resulted in biological changes consistent with the expected biological responses of increased MPC activity, confirming the annotation of these genes as a MPC in intraerythrocytic P. falciparum parasites. National Research Foundation (NRF) Biochemistry, Genetics and Microbiology (BGM) MSc (Biochemistry) Unrestricted Faculty of Natural and Agricultural Sciences SDG-03: Good health and well-being SDG-04: Quality education SDG-09: Industry, innovation and infrastructure 2025-02-14T19:53:08Z 2025-02-14T19:53:08Z 2025-05 2024-11 Dissertation * http://hdl.handle.net/2263/100949 10.25403/UPresearchdata.28387163 en © 2023 University of Pretoria. All rights reserved. The copyright in this work vests in the University of Pretoria. No part of this work may be reproduced or transmitted in any form or by any means, without the prior written permission of the University of Pretoria. application/pdf University of Pretoria |
| spellingShingle | UCTD Sustainable Development Goals (SDGs) Plasmodium falciparum Metabolism Overexpression Mitochondrial pyruvate carrier heterocomplex (MPC) Transgenic The effect of mpc1/mpc2 overexpression in intraerythrocytic Plasmodium falciparum parasites |
| title | The effect of mpc1/mpc2 overexpression in intraerythrocytic Plasmodium falciparum parasites |
| title_full | The effect of mpc1/mpc2 overexpression in intraerythrocytic Plasmodium falciparum parasites |
| title_fullStr | The effect of mpc1/mpc2 overexpression in intraerythrocytic Plasmodium falciparum parasites |
| title_full_unstemmed | The effect of mpc1/mpc2 overexpression in intraerythrocytic Plasmodium falciparum parasites |
| title_short | The effect of mpc1/mpc2 overexpression in intraerythrocytic Plasmodium falciparum parasites |
| title_sort | effect of mpc1 mpc2 overexpression in intraerythrocytic plasmodium falciparum parasites |
| topic | UCTD Sustainable Development Goals (SDGs) Plasmodium falciparum Metabolism Overexpression Mitochondrial pyruvate carrier heterocomplex (MPC) Transgenic |
| url | http://hdl.handle.net/2263/100949 |