ArticlePLoS pathogens2014
BCKDH: the missing link in apicomplexan mitochondrial metabolism is required for full virulence of Toxoplasma gondii and Plasmodium berghei.
Article in PLoS pathogens, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.
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Who cites it
78 citing papers in PubMed, 156 citations in OpenAlex.
- Mitochondrial proteome of the apicomplexan Babesia divergens.Current biology : CB · 2026Article
- Transporters, an important but poorly studied area of Toxoplasma gondii.Parasites & vectors · 2026Review
- Integrative transcriptomic and machine learning approaches to decipher mitochondrial gene regulation in severe Plasmodium vivax malaria.Malaria journal · 2025Article
- Targeting Mitochondrial Function inInternational journal of molecular sciences · 2025Review
- Metabolic crosstalk between the mitochondrion and the nucleus is essential for Toxoplasma gondii infection.Communications biology · 2025Article
- The apicoplast localized isocitrate dehydrogenase is needed forFrontiers in cellular and infection microbiology · 2025Article
- Mitochondria of a human skeletal muscle cell line associate with the parasitophorous vacuoles of three archetypal lineages ofFEMS microbes · 2025Article
- Identification and characterization of thiamine analogs with antiplasmodial activity.Antimicrobial agents and chemotherapy · 2024Article
- TgLaforin, a glucan phosphatase, reveals the dynamic role of storage polysaccharides inbioRxiv : the preprint server for biology · 2024Article
- An endoplasmic reticulum localized acetyl-CoA transporter is required for efficient fatty acid synthesis inOpen biology · 2024Article
- Purinergic Receptor Antagonists Inhibit Hemolysis Induced byPathogens (Basel, Switzerland) · 2024Article
- Protein Lactylation and Metabolic Regulation of the Zoonotic Parasite Toxoplasma gondii.Genomics, proteomics & bioinformatics · 2023Article
- Unique Properties of Apicomplexan Mitochondria.Annual review of microbiology · 2023Review
- Article
- PP2Acα-B'/PR61 Holoenzyme of Toxoplasma gondii Is Required for the Amylopectin Metabolism and Proliferation of Tachyzoites.Microbiology spectrum · 2023Article
- The mitochondrion ofProceedings of the National Academy of Sciences of the United States of America · 2023Article
- Regulation of Mitochondrial Energy Metabolism by Glutaredoxin 5 in the Apicomplexan Parasite Neospora caninum.Microbiology spectrum · 2023Article
- Protein kinases on carbon metabolism: potential targets for alternative chemotherapies against toxoplasmosis.Frontiers in cellular and infection microbiology · 2023Review
- Parasite powerhouse: A review of the Toxoplasma gondii mitochondrion.The Journal of eukaryotic microbiology · 2022Review
- Toxoplasma metabolic flexibility in different growth conditions.Trends in parasitology · 2022Review
18 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 6 institutions in 4 countries.
Funding
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.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.