PDHE3I

PDHE3I is a subunit of the single pyruvate dehydrogenase complex (PDH) in Toxoplasma gondii, an enzyme that is exclusively localised within the apicoplast and absent from the mitochondrion (PMID:18336823). In this compartment-restricted role, the PDH complex generates the apicoplast acetyl-CoA pool that feeds apicoplast fatty acid synthesis, a pool functionally distinct from the cytosolic pool supplied by ACL/ACS and from the mitochondrial pool generated by the BCKDH complex, which functionally replaces mitochondrial PDH in this parasite (PMID:25032958, PMID:32546260). Beyond its identity as a PDH subunit and the apicoplast localisation and metabolic role of the complex it belongs to, nothing further about PDHE3I itself is characterized in the available corpus.

1. 2008 Medium

   Establishing where the T. gondii PDH complex operates was needed because in most eukaryotes PDH is mitochondrial; the finding that this complex, including PDHE3I, is exclusively apicoplast-localised redefined the compartmental logic of acetyl-CoA generation in the parasite.

   Evidence Epitope-tagged fusion protein expression and subcellular localisation of PDH subunits

   PMID:18336823

   Open questions at the time

   • Does not resolve the specific catalytic contribution of PDHE3I within the complex
   • No structural or biochemical characterization of PDHE3I itself
2. 2014 Medium

   It was unknown what supplies mitochondrial acetyl-CoA if PDH is apicoplast-restricted; genetic deletion of BCKDH E1α showed BCKDH functionally replaces mitochondrial PDH, confirming PDH does not perform mitochondrial pyruvate-to-acetyl-CoA conversion.

   Evidence Genetic deletion of BCKDH E1α with isotope tracing/metabolomics and growth/virulence assays; PDH apicoplast localisation used as established context

   PMID:25032958

   Open questions at the time

   • PDH itself was not directly manipulated in this study
   • The specific role of PDHE3I in the complex is not addressed
3. 2020 Medium

   The metabolic destination of apicoplast PDH activity was unclear; multi-omics of ACL/ACS and BCKDH knockouts showed the PDH-derived apicoplast acetyl-CoA pool feeds fatty acid synthesis and is distinct from cytosolic and mitochondrial pools.

   Evidence Multi-omics (acetylome, transcriptome, proteome, metabolome) of conditional knockouts with metabolic flux and fatty acid profiling

   PMID:32546260

   Open questions at the time

   • PDH role inferred from comparative knockouts rather than direct PDH or PDHE3I manipulation
   • The catalytic and regulatory contribution of PDHE3I specifically is not defined