دورية أكاديمية
BCKDH : the missing link in apicomplexan mitochondrial metabolism is required for full virulence of Toxoplasma gondii and Plasmodium berghei
| العنوان: | BCKDH : the missing link in apicomplexan mitochondrial metabolism is required for full virulence of Toxoplasma gondii and Plasmodium berghei |
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| المؤلفون: | Oppenheim, Rebecca D., Creek, Darren J., Macrae, James I., Modrzynska, Katarzyna K., Pino, Paco, Limenitakis, Julien, Polonais, Valerie, Seeber, Frank, Barrett, Michael P., Billker, Oliver, McConville, Malcolm J., Soldati-Favre, Dominique |
| بيانات النشر: | Wellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom PLOS |
| سنة النشر: | 2014 |
| المجموعة: | Umeå University: Publications (DiVA) |
| مصطلحات موضوعية: | Cell and Molecular Biology, Cell- och molekylärbiologi |
| الوصف: | 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. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| العلاقة: | PLoS Pathogens, 1553-7366, 2014, 10:7; orcid:0000-0003-1716-168x; http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-165856Test; PMID 25032958; ISI:000340551000043 |
| DOI: | 10.1371/journal.ppat.1004263 |
| الإتاحة: | https://doi.org/10.1371/journal.ppat.1004263Test http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-165856Test |
| حقوق: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.1CB82141 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1371/journal.ppat.1004263 |
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