{"gene":"PF3D7_1340800","run_date":"2026-09-08T19:44:17","timeline":{"discoveries":[{"year":2025,"finding":"Genetic knockout of PfMPC1 (PF3D7_1340800), alone or in combination with PfMPC2, caused only minor growth defects in asexual blood-stage P. falciparum despite a substantial reduction in glucose-derived isotopic labeling into acetyl-CoA, demonstrating that PfMPC1 is not individually essential for blood-stage replication and that redundant pyruvate/carbon import routes exist.","method":"Genetic knockout combined with isotopic metabolite tracing (HPLC-MS metabolomics) in asexual blood-stage parasites","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean genetic KO with defined metabolic phenotype and isotopic tracing, single lab, two orthogonal methods (genetics + metabolomics)","pmids":["40398604"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2025,"finding":"Quadruple knockout of PfMPC1, PfMPC2, DTC, and YHM2 did not further reduce glucose carbon incorporation into acetyl-CoA compared to PfMPC double-KO alone, but caused a large decrease in glutamine-derived label in TCA cycle metabolites, indicating that PfMPC1/2 are the predominant route for glucose-derived pyruvate import while DTC and YHM2 serve as the main importers of glutamine derivatives into the mitochondrion.","method":"Quadruple genetic knockout combined with isotopic metabolite tracing (HPLC-MS) using glucose and glutamine tracers","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — epistatic multi-gene KO with quantitative metabolic readout, single lab, two orthogonal methods","pmids":["40398604"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PfMPC1 (PF3D7_1340800) is a mitochondrial inner-membrane pyruvate carrier in P. falciparum that contributes to glucose-derived pyruvate import for mitochondrial acetyl-CoA synthesis, but is dispensable for asexual blood-stage growth because redundant carboxylic acid transporters can compensate for its loss."},"narrative":{"mechanistic_narrative":"MPC1 (PF3D7_1340800) is a mitochondrial pyruvate carrier that, together with PfMPC2, constitutes the predominant route for importing glucose-derived pyruvate into the P. falciparum mitochondrion for acetyl-CoA synthesis [PMID:40398604]. Genetic knockout of PfMPC1, alone or combined with PfMPC2, substantially reduces glucose-derived isotopic labeling of acetyl-CoA yet causes only minor asexual blood-stage growth defects, establishing that PfMPC1 is not individually essential and that redundant carbon-import routes compensate for its loss [PMID:40398604]. Epistatic knockout combining PfMPC1/2 with the carboxylic acid transporters DTC and YHM2 does not further diminish glucose carbon incorporation into acetyl-CoA but sharply reduces glutamine-derived labeling of TCA cycle metabolites, defining a division of labor in which PfMPC1/2 handle glucose-derived pyruvate import while DTC and YHM2 import glutamine derivatives [PMID:40398604]. Beyond this genetic and metabolic characterization of its transport role in blood-stage parasites, no further structural or biochemical detail for PfMPC1 has been characterized in the available corpus.","teleology":[{"year":2025,"claim":"It was unknown whether PfMPC1 is required for pyruvate import and blood-stage growth; knockout showed it contributes to glucose-derived acetyl-CoA synthesis but is genetically dispensable, establishing functional redundancy in mitochondrial carbon import.","evidence":"Genetic knockout of PfMPC1 alone and with PfMPC2, plus HPLC-MS isotopic metabolite tracing in asexual blood-stage parasites","pmids":["40398604"],"confidence":"Medium","gaps":["Direct biochemical demonstration of pyruvate transport by PfMPC1 (e.g. reconstitution) is not shown","The identity of the redundant carbon-import routes compensating for PfMPC1 loss is not fully resolved","Role in non-blood-stage or transmission stages not addressed"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2025,"claim":"To distinguish glucose- versus glutamine-derived carbon routes, quadruple knockout established that PfMPC1/2 are the main glucose-derived pyruvate importers while DTC and YHM2 dominate glutamine-derivative import, partitioning mitochondrial substrate supply.","evidence":"Quadruple genetic knockout (PfMPC1, PfMPC2, DTC, YHM2) with glucose and glutamine isotopic tracers analyzed by HPLC-MS","pmids":["40398604"],"confidence":"Medium","gaps":["Individual contribution of PfMPC1 versus PfMPC2 within the pair not separately quantified in the quadruple background","Whether PfMPC1 physically forms a heterocomplex with PfMPC2 is not demonstrated","Direct transport substrate specificity not measured biochemically"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"Whether PfMPC1 assembles into a defined carrier complex, its structure, and its role beyond asexual blood stages remain unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No structural model or biochemical reconstitution of PfMPC1 transport activity","Direct evidence of a physical PfMPC1-PfMPC2 complex not established in the corpus","Stage-specific requirement (gametocyte/mosquito stages) uncharacterized"],"attribution":[]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["PFMPC2 (FUNCTIONALLY REDUNDANT PYRUVATE CARRIER PARTNER)"],"other_free_text":["Genetically dispensable for asexual blood-stage growth despite reduced glucose-derived acetyl-CoA labeling [#0]","Acts in parallel with the carboxylic acid transporters DTC and YHM2, which instead dominate glutamine-derivative import [#1]"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"40398604","id":"PMC_40398604","title":"Multiple, redundant carboxylic acid transporters support mitochondrial metabolism in Plasmodium falciparum.","date":"2025","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/40398604","citation_count":2,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PfMPC1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"39651245","id":"PMC_39651245","title":"MULTIPLE, REDUNDANT CARBOXYLIC ACID TRANSPORTERS SUPPORT MITOCHONDRIAL METABOLISM IN PLASMODIUM FALCIPARUM.","date":"2024","source":"bioRxiv : the preprint server for biology","url":"https://pubmed.ncbi.nlm.nih.gov/39651245","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PfMPC1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"39880906","id":"","title":"Pivotal roles of Plasmodium falciparum lysophospholipid acyltransferase 1 in cell cycle progression and cytostome internalization.","date":"2025","source":"Communications biology","url":"https://pubmed.ncbi.nlm.nih.gov/39880906","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["MPC1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":5592,"output_tokens":675,"usd":0.013451,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5343,"output_tokens":1734,"usd":0.035033,"stage2_stop_reason":"end_turn"},"total_usd":0.048484,"stage1_batch_id":"msgbatch_01SRp5hyRc82zNjddxyCCXGk","stage2_batch_id":"msgbatch_01K3BTmBazRo3pRrMvyaPMTY","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2025,\n      \"finding\": \"Genetic knockout of PfMPC1 (PF3D7_1340800), alone or in combination with PfMPC2, caused only minor growth defects in asexual blood-stage P. falciparum despite a substantial reduction in glucose-derived isotopic labeling into acetyl-CoA, demonstrating that PfMPC1 is not individually essential for blood-stage replication and that redundant pyruvate/carbon import routes exist.\",\n      \"method\": \"Genetic knockout combined with isotopic metabolite tracing (HPLC-MS metabolomics) in asexual blood-stage parasites\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean genetic KO with defined metabolic phenotype and isotopic tracing, single lab, two orthogonal methods (genetics + metabolomics)\",\n      \"pmids\": [\"40398604\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"Quadruple knockout of PfMPC1, PfMPC2, DTC, and YHM2 did not further reduce glucose carbon incorporation into acetyl-CoA compared to PfMPC double-KO alone, but caused a large decrease in glutamine-derived label in TCA cycle metabolites, indicating that PfMPC1/2 are the predominant route for glucose-derived pyruvate import while DTC and YHM2 serve as the main importers of glutamine derivatives into the mitochondrion.\",\n      \"method\": \"Quadruple genetic knockout combined with isotopic metabolite tracing (HPLC-MS) using glucose and glutamine tracers\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — epistatic multi-gene KO with quantitative metabolic readout, single lab, two orthogonal methods\",\n      \"pmids\": [\"40398604\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"PfMPC1 (PF3D7_1340800) is a mitochondrial inner-membrane pyruvate carrier in P. falciparum that contributes to glucose-derived pyruvate import for mitochondrial acetyl-CoA synthesis, but is dispensable for asexual blood-stage growth because redundant carboxylic acid transporters can compensate for its loss.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"MPC1 (PF3D7_1340800) is a mitochondrial pyruvate carrier that, together with PfMPC2, constitutes the predominant route for importing glucose-derived pyruvate into the P. falciparum mitochondrion for acetyl-CoA synthesis [#0, #1]. Genetic knockout of PfMPC1, alone or combined with PfMPC2, substantially reduces glucose-derived isotopic labeling of acetyl-CoA yet causes only minor asexual blood-stage growth defects, establishing that PfMPC1 is not individually essential and that redundant carbon-import routes compensate for its loss [#0]. Epistatic knockout combining PfMPC1/2 with the carboxylic acid transporters DTC and YHM2 does not further diminish glucose carbon incorporation into acetyl-CoA but sharply reduces glutamine-derived labeling of TCA cycle metabolites, defining a division of labor in which PfMPC1/2 handle glucose-derived pyruvate import while DTC and YHM2 import glutamine derivatives [#1]. Beyond this genetic and metabolic characterization of its transport role in blood-stage parasites, no further structural or biochemical detail for PfMPC1 has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2025,\n      \"claim\": \"It was unknown whether PfMPC1 is required for pyruvate import and blood-stage growth; knockout showed it contributes to glucose-derived acetyl-CoA synthesis but is genetically dispensable, establishing functional redundancy in mitochondrial carbon import.\",\n      \"evidence\": \"Genetic knockout of PfMPC1 alone and with PfMPC2, plus HPLC-MS isotopic metabolite tracing in asexual blood-stage parasites\",\n      \"pmids\": [\"40398604\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Direct biochemical demonstration of pyruvate transport by PfMPC1 (e.g. reconstitution) is not shown\",\n        \"The identity of the redundant carbon-import routes compensating for PfMPC1 loss is not fully resolved\",\n        \"Role in non-blood-stage or transmission stages not addressed\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"To distinguish glucose- versus glutamine-derived carbon routes, quadruple knockout established that PfMPC1/2 are the main glucose-derived pyruvate importers while DTC and YHM2 dominate glutamine-derivative import, partitioning mitochondrial substrate supply.\",\n      \"evidence\": \"Quadruple genetic knockout (PfMPC1, PfMPC2, DTC, YHM2) with glucose and glutamine isotopic tracers analyzed by HPLC-MS\",\n      \"pmids\": [\"40398604\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Individual contribution of PfMPC1 versus PfMPC2 within the pair not separately quantified in the quadruple background\",\n        \"Whether PfMPC1 physically forms a heterocomplex with PfMPC2 is not demonstrated\",\n        \"Direct transport substrate specificity not measured biochemically\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Whether PfMPC1 assembles into a defined carrier complex, its structure, and its role beyond asexual blood stages remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No structural model or biochemical reconstitution of PfMPC1 transport activity\",\n        \"Direct evidence of a physical PfMPC1-PfMPC2 complex not established in the corpus\",\n        \"Stage-specific requirement (gametocyte/mosquito stages) uncharacterized\"\n      ],\n      \"attribution\": []\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0050833\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005743\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0006090\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"PfMPC2 (functionally redundant pyruvate carrier partner)\"],\n    \"other_free_text\": [\n      \"Genetically dispensable for asexual blood-stage growth despite reduced glucose-derived acetyl-CoA labeling [#0]\",\n      \"Acts in parallel with the carboxylic acid transporters DTC and YHM2, which instead dominate glutamine-derivative import [#1]\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1340800","name":null,"product":"mitochondrial pyruvate carrier protein 1, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1354200","name":null,"product":"mitochondrial pyruvate carrier protein 1, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1260600","name":null,"product":"mitochondrial pyruvate carrier protein 1, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"MPC1","evaluation":null}