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Title

Contribution of the TCA cycle in the central carbon metabolism of apicomplexan parasites
Author
Oppenheim, Rebecca
Directors
Soldati-Favre, Dominique
Martinou, Jean-Claude
Defense Thèse de doctorat : Univ. Genève, 2015 - Sc. 4858 - 2015/11/19
Abstract The absence of mitochondrial pyruvate dehydrogenase complex had failed to establish a link between glycolysis and mitochondrial carboxylic acid metabolism and posed a dilemma regarding the possible alternative source(s) of mitochondrial acetyl-CoA to fuel a canonical oxidative TCA cycle in the apicomplexan parasites such as Toxoplasma gondii and Plasmodium species. Using a combination of reverse genetics and metabolic profiling by mass spectrometry, we have established that the branched chain amino acid (BCAA) degradation pathway and the 2-methylcitrate cycle which detoxifies propionyl-CoA concomitantly produced during BCAAs degradation are both dispensable and not the source of mitochondrial acetyl-CoA for these parasites. Rather we provide evidence that the BCKDH complex has evolved towards the use of glycolytic pyruvate and act as a substitute for the PDH complex to generate mitochondrial acetyl-CoA and sustain a complete TCA cycle. Furthermore, we investigated the routes to generate cytoplasmic acetyl-CoA and their importance in T. gondii.
Keywords Toxoplasma gondii — Plasmodium species — Mitochondrion — Apicoplast — Central carbon metabolism — Acetyl-CoA — TCA cycle — 2-methycitrate cycle — Branched chain ketoacid dehydrogenase complex
Identifiers
URN: urn:nbn:ch:unige-801562
Full text
Thesis (6.2 MB) - public document Free access
Structures
Faculté des sciences / Section de biologie / Département de biologie cellulaire
Faculté de médecine / Section de médecine fondamentale / Département de microbiologie et médecine moléculaire
Citation
(ISO format) 		OPPENHEIM, Rebecca. Contribution of the TCA cycle in the central carbon metabolism of apicomplexan parasites. Université de Genève. Thèse, 2015. https://archive-ouverte.unige.ch/unige:80156

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Deposited on : 2016-02-01

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