Affinage · Toxoplasma gondii

PDHE1A

pyruvate dehydrogenase complex subunit PDH-E1Alpha · UniProt S8ENF7

Annotated
2026-09-10
5 papers in source corpus 3 papers cited in narrative 3 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PDHE1A is the E1Alpha subunit of the pyruvate dehydrogenase complex (PDH) in Toxoplasma gondii, where it functions within an apicoplast-based pathway that converts pyruvate into the acetyl-CoA pool used for de novo fatty acid biosynthesis (PMID:18336823, PMID:32341123). In contrast to the mitochondrial PDH of most eukaryotes, this complex localizes exclusively to the apicoplast and is absent from the mitochondrion (PMID:18336823). The apicoplast PDH generates a distinct, compartment-specific acetyl-CoA pool dedicated to the FAS2 pathway (PMID:32546260), and CRISPR/Cas9 deletion of pdh-e1α reduces incorporation of glucose-derived carbon into medium-chain fatty acids (C14:0 and C16:0), producing parasites with impaired growth and loss of the apicoplast while retaining normal virulence in mice owing to salvage of host-derived fatty acids (PMID:32341123). Nothing further about PDHE1A has been characterized in the available corpus.

Mechanistic history

Synthesis pass · year-by-year structured walk · 3 steps
  1. 2008 Medium

    Establishing where PDH operates in T. gondii was needed because the canonical PDH is mitochondrial; localizing the complex fixed the compartment in which PDHE1A acts.

    Evidence Expression of epitope-tagged fusion proteins and subcellular localization

    PMID:18336823

    Open questions at the time
    • Localization based on tagged fusion proteins in a single lab
    • Does not establish the metabolic function of the compartmentalized complex
  2. 2020 High

    Whether apicoplast PDH actually drives fatty acid synthesis and is essential was unresolved; direct deletion showed PDHE1A supplies carbon for de novo fatty acid biosynthesis and is required for apicoplast maintenance but dispensable in vivo via host lipid salvage.

    Evidence CRISPR/Cas9 deletion of pdh-e1α, glucose metabolic labeling, fatty acid supplementation rescue, and mouse virulence assay

    PMID:32341123

    Open questions at the time
    • Mechanism of apicoplast loss upon deletion not resolved
    • Enzymatic parameters of the PDHE1A subunit not defined
  3. 2020 Medium

    It was unclear whether apicoplast PDH provides a functionally distinct acetyl-CoA pool; multi-omics of mutants in other acetyl-CoA enzymes confirmed the PDH-derived pool is compartment-specific and dedicated to fatty acid synthesis.

    Evidence Multi-omics (acetylome, transcriptome, proteome, metabolome) of parasites lacking other acetyl-CoA-generating enzymes

    PMID:32546260

    Open questions at the time
    • PDH role inferred from complementary mutants rather than direct PDH KO in this study
    • Does not resolve regulation of the PDH pool

Mechanism profile

Synthesis pass · controlled-vocabulary classification
Complex memberships
Pyruvate dehydrogenase complex (apicoplast PDH)

Evidence

Reading pass · 3 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2008 The pyruvate dehydrogenase complex (PDH), which includes the E1Alpha subunit (PDHE1A), is exclusively localised inside the apicoplast of T. gondii and is absent from the mitochondrion, as determined by expression of epitope-tagged fusion proteins. Epitope-tagged fusion protein expression and subcellular localization International journal for parasitology Medium 18336823
2020 CRISPR/Cas9-assisted deletion of the pdh-e1α gene (PDHE1A) in T. gondii tachyzoites produced viable parasites with impaired growth and concurrent loss of the apicoplast, but normal virulence in mice; metabolic labeling of the Δpdh-e1α mutant showed reduced incorporation of glucose-derived carbon into medium-chain fatty acids (C14:0 and C16:0), demonstrating that apicoplast-localized PDH drives de novo fatty acid biosynthesis via FAS2. CRISPR/Cas9 gene deletion, metabolic labeling, mouse virulence assay, fatty acid supplementation rescue The Journal of biological chemistry High 32341123
2020 The apicoplast pyruvate dehydrogenase complex (PDH), which includes PDHE1A, generates the acetyl-CoA pool dedicated to de novo fatty acid synthesis within the apicoplast; multi-omics profiling of parasites lacking other acetyl-CoA-generating enzymes confirmed the distinct, compartment-specific role of the PDH-derived apicoplast acetyl-CoA pool. Multi-omics (acetylome, transcriptome, proteome, metabolome) of parasite mutants lacking other acetyl-CoA enzymes BMC biology Medium 32546260

Source papers

Stage 0 corpus · 5 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2014 BCKDH: the missing link in apicomplexan mitochondrial metabolism is required for full virulence of Toxoplasma gondii and Plasmodium berghei. PLoS pathogens 102 25032958
2008 Localisation of gluconeogenesis and tricarboxylic acid (TCA)-cycle enzymes and first functional analysis of the TCA cycle in Toxoplasma gondii. International journal for parasitology 43 18336823
2020 Acquisition of exogenous fatty acids renders apicoplast-based biosynthesis dispensable in tachyzoites of Toxoplasma. The Journal of biological chemistry 42 32341123
2020 Multi-omics analysis delineates the distinct functions of sub-cellular acetyl-CoA pools in Toxoplasma gondii. BMC biology 39 32546260
2021 Dichloroacetate and Pyruvate Metabolism: Pyruvate Dehydrogenase Kinases as Targets Worth Investigating for Effective Therapy of Toxoplasmosis. mSphere 9 33408226