{"gene":"TG_305980","gene_symbol":"PDHE3I","run_date":"2026-09-10T21:09:19","timeline":{"discoveries":[{"year":2008,"finding":"The pyruvate dehydrogenase complex (PDH) in T. gondii, which includes PDHE3I as a subunit, is exclusively localised inside the apicoplast and is absent from the mitochondrion, as demonstrated by localisation of epitope-tagged fusion proteins.","method":"Epitope-tagged fusion protein expression and subcellular localisation","journal":"International journal for parasitology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct localization experiment with epitope-tagged proteins, single lab, finding replicated by subsequent studies referencing apicoplast-exclusive PDH localization","pmids":["18336823"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2014,"finding":"The pyruvate dehydrogenase complex (PDH), which includes PDHE3I, is exclusively apicoplast-localised and does not catalyse mitochondrial pyruvate-to-acetyl-CoA conversion; instead, the mitochondrial branched-chain ketoacid dehydrogenase (BCKDH) complex functionally replaces mitochondrial PDH in T. gondii.","method":"Genetic deletion of BCKDH E1α subunit combined with metabolic profiling (isotope tracing/metabolomics) and growth/virulence assays; apicoplast localization of PDH referenced as established context","journal":"PLoS pathogens","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — functional and metabolic evidence from knockout parasites in single study; PDH apicoplast localisation is cited as established context, not re-demonstrated here","pmids":["25032958"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2020,"finding":"The apicoplast pyruvate dehydrogenase complex (PDH), which includes PDHE3I, generates the apicoplast acetyl-CoA pool required for fatty acid synthesis; the cytosolic acetyl-CoA pool (from ACL/ACS) is essential for fatty acid elongation, while the PDH-derived apicoplast pool is functionally distinct from the mitochondrial pool generated by BCKDH.","method":"Multi-omics analysis (acetylome, transcriptome, proteome, metabolome) of conditional knockouts of ACL/ACS and BCKDH, with metabolic flux and fatty acid profiling","journal":"BMC biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multi-omics with multiple orthogonal methods in a single lab study; PDH complex role inferred from comparative knockouts rather than direct PDH manipulation","pmids":["32546260"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"current_model":"PDHE3I is a subunit of the sole pyruvate dehydrogenase complex (PDH) in Toxoplasma gondii, which is exclusively localised to the apicoplast (not the mitochondrion) and generates the apicoplast acetyl-CoA pool required for apicoplast fatty acid synthesis, while mitochondrial acetyl-CoA production is instead carried out by the BCKDH complex."},"narrative":{"mechanistic_narrative":"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.","teleology":[{"year":2008,"claim":"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","pmids":["18336823"],"confidence":"Medium","gaps":["Does not resolve the specific catalytic contribution of PDHE3I within the complex","No structural or biochemical characterization of PDHE3I itself"],"attribution":[]},{"year":2014,"claim":"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","pmids":["25032958"],"confidence":"Medium","gaps":["PDH itself was not directly manipulated in this study","The specific role of PDHE3I in the complex is not addressed"],"attribution":[]},{"year":2020,"claim":"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","pmids":["32546260"],"confidence":"Medium","gaps":["PDH role inferred from comparative knockouts rather than direct PDH or PDHE3I manipulation","The catalytic and regulatory contribution of PDHE3I specifically is not defined"],"attribution":[]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["Pyruvate dehydrogenase complex (apicoplast PDH)"],"partners":[],"other_free_text":["PDHE3I is a subunit of the sole T. gondii PDH complex, which is apicoplast-localised rather than mitochondrial [#0].","The apicoplast PDH complex generates the acetyl-CoA pool used for apicoplast fatty acid synthesis, distinct from cytosolic (ACL/ACS) and mitochondrial (BCKDH) pools [#2]."]},"strain_conflicts":[]},"prefetch_data":{},"corpus_meta":[{"pmid":"25032958","id":"PMC_25032958","title":"BCKDH: the missing link in apicomplexan mitochondrial metabolism is required for full virulence of Toxoplasma gondii and Plasmodium berghei.","date":"2014","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/25032958","citation_count":102,"is_preprint":false},{"pmid":"18336823","id":"PMC_18336823","title":"Localisation of gluconeogenesis and tricarboxylic acid (TCA)-cycle enzymes and first functional analysis of the TCA cycle in Toxoplasma gondii.","date":"2008","source":"International journal for parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/18336823","citation_count":43,"is_preprint":false},{"pmid":"32546260","id":"PMC_32546260","title":"Multi-omics analysis delineates the distinct functions of sub-cellular acetyl-CoA pools in Toxoplasma gondii.","date":"2020","source":"BMC biology","url":"https://pubmed.ncbi.nlm.nih.gov/32546260","citation_count":39,"is_preprint":false},{"pmid":"33408226","id":"PMC_33408226","title":"Dichloroacetate and Pyruvate Metabolism: Pyruvate Dehydrogenase Kinases as Targets Worth Investigating for Effective Therapy of Toxoplasmosis.","date":"2021","source":"mSphere","url":"https://pubmed.ncbi.nlm.nih.gov/33408226","citation_count":9,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":4810,"output_tokens":1399,"usd":0.017708,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6483,"output_tokens":2730,"usd":0.050333,"stage2_stop_reason":"end_turn"},"total_usd":0.121128,"stage1_batch_id":"msgbatch_01S6GjoYQm8LTPUsdhASdqag","stage2_batch_id":"msgbatch_01VX63RTMdBJqsG6gQMqoCjz","note":"batch pricing = 50% of standard","corrective_rerun":"2026-09-10 wrong-gene rerun (round-4 rules)","corrective_reason":"re-read with subject anchor"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2008,\n      \"finding\": \"The pyruvate dehydrogenase complex (PDH) in T. gondii, which includes PDHE3I as a subunit, is exclusively localised inside the apicoplast and is absent from the mitochondrion, as demonstrated by localisation of epitope-tagged fusion proteins.\",\n      \"method\": \"Epitope-tagged fusion protein expression and subcellular localisation\",\n      \"journal\": \"International journal for parasitology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct localization experiment with epitope-tagged proteins, single lab, finding replicated by subsequent studies referencing apicoplast-exclusive PDH localization\",\n      \"pmids\": [\"18336823\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"The pyruvate dehydrogenase complex (PDH), which includes PDHE3I, is exclusively apicoplast-localised and does not catalyse mitochondrial pyruvate-to-acetyl-CoA conversion; instead, the mitochondrial branched-chain ketoacid dehydrogenase (BCKDH) complex functionally replaces mitochondrial PDH in T. gondii.\",\n      \"method\": \"Genetic deletion of BCKDH E1α subunit combined with metabolic profiling (isotope tracing/metabolomics) and growth/virulence assays; apicoplast localization of PDH referenced as established context\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — functional and metabolic evidence from knockout parasites in single study; PDH apicoplast localisation is cited as established context, not re-demonstrated here\",\n      \"pmids\": [\"25032958\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"The apicoplast pyruvate dehydrogenase complex (PDH), which includes PDHE3I, generates the apicoplast acetyl-CoA pool required for fatty acid synthesis; the cytosolic acetyl-CoA pool (from ACL/ACS) is essential for fatty acid elongation, while the PDH-derived apicoplast pool is functionally distinct from the mitochondrial pool generated by BCKDH.\",\n      \"method\": \"Multi-omics analysis (acetylome, transcriptome, proteome, metabolome) of conditional knockouts of ACL/ACS and BCKDH, with metabolic flux and fatty acid profiling\",\n      \"journal\": \"BMC biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multi-omics with multiple orthogonal methods in a single lab study; PDH complex role inferred from comparative knockouts rather than direct PDH manipulation\",\n      \"pmids\": [\"32546260\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"PDHE3I is a subunit of the sole pyruvate dehydrogenase complex (PDH) in Toxoplasma gondii, which is exclusively localised to the apicoplast (not the mitochondrion) and generates the apicoplast acetyl-CoA pool required for apicoplast fatty acid synthesis, while mitochondrial acetyl-CoA production is instead carried out by the BCKDH complex.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"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 [#0]. 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 [#1, #2]. 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.\",\n  \"teleology\": [\n    {\n      \"year\": 2008,\n      \"claim\": \"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.\",\n      \"evidence\": \"Epitope-tagged fusion protein expression and subcellular localisation of PDH subunits\",\n      \"pmids\": [\"18336823\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Does not resolve the specific catalytic contribution of PDHE3I within the complex\", \"No structural or biochemical characterization of PDHE3I itself\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"It was unknown what supplies mitochondrial acetyl-CoA if PDH is apicoplast-restricted; genetic deletion of BCKDH E1\\u03b1 showed BCKDH functionally replaces mitochondrial PDH, confirming PDH does not perform mitochondrial pyruvate-to-acetyl-CoA conversion.\",\n      \"evidence\": \"Genetic deletion of BCKDH E1\\u03b1 with isotope tracing/metabolomics and growth/virulence assays; PDH apicoplast localisation used as established context\",\n      \"pmids\": [\"25032958\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"PDH itself was not directly manipulated in this study\", \"The specific role of PDHE3I in the complex is not addressed\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"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.\",\n      \"evidence\": \"Multi-omics (acetylome, transcriptome, proteome, metabolome) of conditional knockouts with metabolic flux and fatty acid profiling\",\n      \"pmids\": [\"32546260\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"PDH role inferred from comparative knockouts rather than direct PDH or PDHE3I manipulation\", \"The catalytic and regulatory contribution of PDHE3I specifically is not defined\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The specific molecular function, structure, and regulation of the PDHE3I subunit within the apicoplast PDH complex remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No direct genetic or biochemical characterization of PDHE3I alone\", \"No structural model of PDHE3I\", \"Its essentiality independent of the whole complex is unknown\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0004739\", \"supporting_discovery_ids\": [0, 1, 2], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0020011\", \"supporting_discovery_ids\": [0, 1], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0006633\", \"supporting_discovery_ids\": [2], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]},\n      {\"term_id\": \"GO:0006086\", \"supporting_discovery_ids\": [0, 1, 2], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"complexes\": [\"Pyruvate dehydrogenase complex (apicoplast PDH)\"],\n    \"partners\": [],\n    \"other_free_text\": [\n      \"PDHE3I is a subunit of the sole T. gondii PDH complex, which is apicoplast-localised rather than mitochondrial [#0].\",\n      \"The apicoplast PDH complex generates the acetyl-CoA pool used for apicoplast fatty acid synthesis, distinct from cytosolic (ACL/ACS) and mitochondrial (BCKDH) pools [#2].\"\n    ]\n  },\n  \"strain_conflicts\": []\n}\n```","audit_flag":null,"strains":[{"strain":"ME49","gene_id":"TGME49_305980","name":"PDHE3I","product":"pyruvate dehydrogenase complex subunit PDH-E3I","uniprot_acc":"S8GG49","chromosome":"TGME49_chrIX","start_pos":5705046},{"strain":"GT1","gene_id":"TGGT1_305980","name":null,"product":"pyruvate dehydrogenase complex subunit PDH-E3I","uniprot_acc":null,"chromosome":"TGGT1_chrIX","start_pos":5486775},{"strain":"RH88","gene_id":"TGRH88_017520","name":null,"product":"pyruvate dehydrogenase complex subunit PDH-E3I","uniprot_acc":null,"chromosome":"CM023090","start_pos":5828394},{"strain":"VEG","gene_id":"TGVEG_305980","name":null,"product":"pyruvate dehydrogenase complex subunit PDH-E3I","uniprot_acc":"A0A125YHJ5","chromosome":"TGVEG_chrIX","start_pos":5743803}]}