BCKDH: the missing link in apicomplexan mitochondrial metabolism is required for full virulence of Toxoplasma gondii and Plasmodium berghei.

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 d...

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Autores principales:	Rebecca D Oppenheim, Darren J Creek, James I Macrae, Katarzyna K Modrzynska, Paco Pino, Julien Limenitakis, Valerie Polonais, Frank Seeber, Michael P Barrett, Oliver Billker, Malcolm J McConville, Dominique Soldati-Favre
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/ab0ccab8afb741458ebb221efccb6aaa
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spelling	oai:doaj.org-article:ab0ccab8afb741458ebb221efccb6aaa2021-11-25T05:46:16ZBCKDH: the missing link in apicomplexan mitochondrial metabolism is required for full virulence of Toxoplasma gondii and Plasmodium berghei.1553-73661553-737410.1371/journal.ppat.1004263https://doaj.org/article/ab0ccab8afb741458ebb221efccb6aaa2014-07-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/25032958/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374While 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.Rebecca D OppenheimDarren J CreekJames I MacraeKatarzyna K ModrzynskaPaco PinoJulien LimenitakisValerie PolonaisFrank SeeberMichael P BarrettOliver BillkerMalcolm J McConvilleDominique Soldati-FavrePublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 10, Iss 7, p e1004263 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Rebecca D Oppenheim Darren J Creek James I Macrae Katarzyna K Modrzynska Paco Pino Julien Limenitakis Valerie Polonais Frank Seeber Michael P Barrett Oliver Billker Malcolm J McConville Dominique Soldati-Favre BCKDH: the missing link in apicomplexan mitochondrial metabolism is required for full virulence of Toxoplasma gondii and Plasmodium berghei.
description	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.
format	article
author	Rebecca D Oppenheim Darren J Creek James I Macrae Katarzyna K Modrzynska Paco Pino Julien Limenitakis Valerie Polonais Frank Seeber Michael P Barrett Oliver Billker Malcolm J McConville Dominique Soldati-Favre
author_facet	Rebecca D Oppenheim Darren J Creek James I Macrae Katarzyna K Modrzynska Paco Pino Julien Limenitakis Valerie Polonais Frank Seeber Michael P Barrett Oliver Billker Malcolm J McConville Dominique Soldati-Favre
author_sort	Rebecca D Oppenheim
title	BCKDH: the missing link in apicomplexan mitochondrial metabolism is required for full virulence of Toxoplasma gondii and Plasmodium berghei.
title_short	BCKDH: the missing link in apicomplexan mitochondrial metabolism is required for full virulence of Toxoplasma gondii and Plasmodium berghei.
title_full	BCKDH: the missing link in apicomplexan mitochondrial metabolism is required for full virulence of Toxoplasma gondii and Plasmodium berghei.
title_fullStr	BCKDH: the missing link in apicomplexan mitochondrial metabolism is required for full virulence of Toxoplasma gondii and Plasmodium berghei.
title_full_unstemmed	BCKDH: the missing link in apicomplexan mitochondrial metabolism is required for full virulence of Toxoplasma gondii and Plasmodium berghei.
title_sort	bckdh: the missing link in apicomplexan mitochondrial metabolism is required for full virulence of toxoplasma gondii and plasmodium berghei.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/ab0ccab8afb741458ebb221efccb6aaa
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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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