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English

BCKDH: The Missing Link in Apicomplexan Mitochondrial Metabolism Is Required for Full Virulence of Toxoplasma gondii and Plasmodium berghei

Contributors

Oppenheim, Rebecca; Creek, Darren J; Macrae, James I; Modrzynska, Katarzyna K; Pino, Paco; Limenitakis, Julien; Polonais, Valérie; Seeber, Frank; Barrett, Michael P; Billker, Oliver; McConville, Malcolm J; Soldati-Favre, Dominique

Published in

PLOS pathogens, vol. 10, no. 7, e1004263

Publication date

2014

Abstract

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.

UNIGE affiliation entities

UNIGE research groups

Citation (ISO format)

OPPENHEIM, Rebecca et al. BCKDH: The Missing Link in Apicomplexan Mitochondrial Metabolism Is Required for Full Virulence of Toxoplasma gondii and Plasmodium berghei. In: PLOS pathogens, 2014, vol. 10, n° 7, p. e1004263. doi: 10.1371/journal.ppat.1004263

Main files (1)

Article (Accepted version)

Identifiers

Journal ISSN

1553-7366
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864downloads

Technical informations

Creation

29/07/2014 18:34:00

First validation

29/07/2014 18:34:00

Update

14/03/2023 21:32:28

Status update

14/03/2023 21:32:27

Last indexation

30/10/2024 19:47:31
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