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BCKDH: the missing link in apicomplexan mitochondrial metabolism is required for full virulence of Toxoplasma gondii and Plasmodium berghei
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2014 (English)In: PLoS Pathogens, ISSN 1553-7366, E-ISSN 1553-7374, Vol. 10, no 7, article id e1004263Article in journal (Refereed) Published
Abstract [en]

While the apicomplexan parasites Plasmodium falciparum and Toxoplasma gondii are thought to primarily depend on glycolysis for ATP synthesis, recent studies have shown that they can fully catabolize glucose in a canonical TCA cycle. However, these parasites lack a mitochondrial isoform of pyruvate dehydrogenase and the identity of the enzyme that catalyses the conversion of pyruvate to acetyl-CoA remains enigmatic. Here we demonstrate that the mitochondrial branched chain ketoacid dehydrogenase (BCKDH) complex is the missing link, functionally replacing mitochondrial PDH in both T. gondii and P. berghei. Deletion of the E1a subunit of T. gondii and P. berghei BCKDH significantly impacted on intracellular growth and virulence of both parasites. Interestingly, disruption of the P. berghei E1a restricted parasite development to reticulocytes only and completely prevented maturation of oocysts during mosquito transmission. Overall this study highlights the importance of the molecular adaptation of BCKDH in this important class of pathogens.

Place, publisher, year, edition, pages
PLOS , 2014. Vol. 10, no 7, article id e1004263
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Cell and Molecular Biology
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URN: urn:nbn:se:umu:diva-165856DOI: 10.1371/journal.ppat.1004263ISI: 000340551000043PubMedID: 25032958OAI: oai:DiVA.org:umu-165856DiVA, id: diva2:1379126
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Wellcome trustAvailable from: 2019-12-16 Created: 2019-12-16 Last updated: 2019-12-18Bibliographically approved

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