{"gene":"PF3D7_1470400","run_date":"2026-09-08T14:19:07","timeline":{"discoveries":[{"year":2025,"finding":"Genetic knockout of PfMPC2 (PF3D7_1470400), alone or in combination with PfMPC1, 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 PfMPC2 contributes to mitochondrial pyruvate import and downstream acetyl-CoA synthesis but is dispensable due to redundant carbon import routes.","method":"Genetic knockout combined with isotopic metabolite tracing via HPLC-MS metabolomics","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 with two orthogonal methods (KO + metabolomics)","pmids":["40398604"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2024,"finding":"Genetic knockout of PfMPC2 (PF3D7_1470400), alone or combined with PfMPC1 knockout, resulted in only minor blood-stage replication defects with a substantial reduction in glucose-derived isotopic labeling into acetyl-CoA, confirming PfMPC2's role in mitochondrial pyruvate import while revealing functional redundancy with other carboxylic acid transporters (DTC, YHM2).","method":"Genetic knockout and isotopic metabolite tracing via HPLC-MS metabolomics (preprint)","journal":"bioRxiv","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean genetic KO with isotopic tracing, single lab; preprint version of subsequently published peer-reviewed study","pmids":["39651245"],"is_preprint":true,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PfMPC2 (PF3D7_1470400) is a mitochondrial pyruvate carrier protein in P. falciparum that contributes to the import of glycolytic pyruvate across the mitochondrial inner membrane for acetyl-CoA synthesis, but is functionally dispensable in asexual blood-stage parasites due to redundant carboxylic acid transport routes involving DTC and YHM2."},"narrative":{"mechanistic_narrative":"MPC2 (PF3D7_1470400) is a mitochondrial pyruvate carrier protein in Plasmodium falciparum that contributes to the import of glycolytic pyruvate across the mitochondrial inner membrane for downstream acetyl-CoA synthesis [PMID:40398604]. Genetic knockout of MPC2, alone or in combination with PfMPC1, causes only minor growth defects in asexual blood-stage parasites despite a substantial reduction in glucose-derived isotopic labeling into acetyl-CoA, establishing that MPC2 participates in mitochondrial pyruvate import but is functionally dispensable because of redundant carboxylic acid transport routes attributed to DTC and YHM2 [PMID:40398604]. Beyond this metabolic role in pyruvate import and the demonstration of transporter redundancy, no further mechanistic detail—including biochemical transport activity, structural features, or interaction partners of MPC2 itself—has been characterized in the available corpus.","teleology":[{"year":2024,"claim":"It was unknown whether MPC2 was required for mitochondrial pyruvate import in blood-stage P. falciparum; knockout combined with isotopic tracing showed MPC2 contributes to pyruvate-derived acetyl-CoA synthesis yet is dispensable, establishing functional redundancy with other carboxylic acid transporters.","evidence":"Genetic knockout of MPC2 (alone and with PfMPC1) with glucose-derived isotopic metabolite tracing by HPLC-MS metabolomics (preprint)","pmids":["39651245"],"confidence":"Medium","gaps":["Direct biochemical demonstration of pyruvate transport by MPC2 not shown","Individual contributions of DTC and YHM2 to the redundant route not resolved","No structural or interaction data for MPC2"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2025,"claim":"The peer-reviewed study confirmed that MPC2 contributes to mitochondrial pyruvate import and downstream acetyl-CoA synthesis but is dispensable in asexual blood-stage parasites due to redundant carbon import routes.","evidence":"Genetic knockout combined with isotopic metabolite tracing via HPLC-MS metabolomics","pmids":["40398604"],"confidence":"Medium","gaps":["Whether MPC2 is required in non-asexual stages (e.g. gametocytes, liver stage) not tested","No reconstituted transport assay defining MPC2 substrate specificity or kinetics","Molecular basis of redundancy with DTC/YHM2 not mechanistically dissected"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"Whether MPC2 acts as a direct pyruvate transporter versus a component of a larger carrier complex, its interaction with PfMPC1, and its stage-specific essentiality remain unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No direct biochemical transport assay for MPC2","MPC2-PfMPC1 physical complex not demonstrated in the corpus","Localization and topology of MPC2 not experimentally established here"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["PFMPC1"],"other_free_text":["Genetic knockout of MPC2 causes only minor asexual blood-stage growth defects, indicating dispensability due to redundant carboxylic acid transport routes attributed to DTC and YHM2 [#0].","MPC2 knockout substantially reduces glucose-derived isotopic labeling into acetyl-CoA, linking MPC2 to mitochondrial pyruvate import and downstream acetyl-CoA synthesis [#0, #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":["PfMPC2"],"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":["PfMPC2"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":4084,"output_tokens":669,"usd":0.011144,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5324,"output_tokens":1649,"usd":0.033923,"stage2_stop_reason":"end_turn"},"total_usd":0.045067,"stage1_batch_id":"msgbatch_011BPjN2BL33F8cJXD1r7V7T","stage2_batch_id":"msgbatch_01Qwg6vP7qxkpL6Gsc7tajsb","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2025,\n      \"finding\": \"Genetic knockout of PfMPC2 (PF3D7_1470400), alone or in combination with PfMPC1, 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 PfMPC2 contributes to mitochondrial pyruvate import and downstream acetyl-CoA synthesis but is dispensable due to redundant carbon import routes.\",\n      \"method\": \"Genetic knockout combined with isotopic metabolite tracing via HPLC-MS metabolomics\",\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 with two orthogonal methods (KO + metabolomics)\",\n      \"pmids\": [\"40398604\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"Genetic knockout of PfMPC2 (PF3D7_1470400), alone or combined with PfMPC1 knockout, resulted in only minor blood-stage replication defects with a substantial reduction in glucose-derived isotopic labeling into acetyl-CoA, confirming PfMPC2's role in mitochondrial pyruvate import while revealing functional redundancy with other carboxylic acid transporters (DTC, YHM2).\",\n      \"method\": \"Genetic knockout and isotopic metabolite tracing via HPLC-MS metabolomics (preprint)\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean genetic KO with isotopic tracing, single lab; preprint version of subsequently published peer-reviewed study\",\n      \"pmids\": [\"39651245\"],\n      \"is_preprint\": true,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"PfMPC2 (PF3D7_1470400) is a mitochondrial pyruvate carrier protein in P. falciparum that contributes to the import of glycolytic pyruvate across the mitochondrial inner membrane for acetyl-CoA synthesis, but is functionally dispensable in asexual blood-stage parasites due to redundant carboxylic acid transport routes involving DTC and YHM2.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"MPC2 (PF3D7_1470400) is a mitochondrial pyruvate carrier protein in Plasmodium falciparum that contributes to the import of glycolytic pyruvate across the mitochondrial inner membrane for downstream acetyl-CoA synthesis [#0]. Genetic knockout of MPC2, alone or in combination with PfMPC1, causes only minor growth defects in asexual blood-stage parasites despite a substantial reduction in glucose-derived isotopic labeling into acetyl-CoA, establishing that MPC2 participates in mitochondrial pyruvate import but is functionally dispensable because of redundant carboxylic acid transport routes attributed to DTC and YHM2 [#0]. Beyond this metabolic role in pyruvate import and the demonstration of transporter redundancy, no further mechanistic detail—including biochemical transport activity, structural features, or interaction partners of MPC2 itself—has been characterized in the available corpus.\"\n  ,\n  \"teleology\": [\n    {\n      \"year\": 2024,\n      \"claim\": \"It was unknown whether MPC2 was required for mitochondrial pyruvate import in blood-stage P. falciparum; knockout combined with isotopic tracing showed MPC2 contributes to pyruvate-derived acetyl-CoA synthesis yet is dispensable, establishing functional redundancy with other carboxylic acid transporters.\",\n      \"evidence\": \"Genetic knockout of MPC2 (alone and with PfMPC1) with glucose-derived isotopic metabolite tracing by HPLC-MS metabolomics (preprint)\",\n      \"pmids\": [\"39651245\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Direct biochemical demonstration of pyruvate transport by MPC2 not shown\",\n        \"Individual contributions of DTC and YHM2 to the redundant route not resolved\",\n        \"No structural or interaction data for MPC2\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"The peer-reviewed study confirmed that MPC2 contributes to mitochondrial pyruvate import and downstream acetyl-CoA synthesis but is dispensable in asexual blood-stage parasites due to redundant carbon import routes.\",\n      \"evidence\": \"Genetic knockout combined with isotopic metabolite tracing via HPLC-MS metabolomics\",\n      \"pmids\": [\"40398604\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Whether MPC2 is required in non-asexual stages (e.g. gametocytes, liver stage) not tested\",\n        \"No reconstituted transport assay defining MPC2 substrate specificity or kinetics\",\n        \"Molecular basis of redundancy with DTC/YHM2 not mechanistically dissected\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Whether MPC2 acts as a direct pyruvate transporter versus a component of a larger carrier complex, its interaction with PfMPC1, and its stage-specific essentiality remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No direct biochemical transport assay for MPC2\",\n        \"MPC2-PfMPC1 physical complex not demonstrated in the corpus\",\n        \"Localization and topology of MPC2 not experimentally established here\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\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\": [\"PfMPC1\"],\n    \"other_free_text\": [\n      \"Genetic knockout of MPC2 causes only minor asexual blood-stage growth defects, indicating dispensability due to redundant carboxylic acid transport routes attributed to DTC and YHM2 [#0].\",\n      \"MPC2 knockout substantially reduces glucose-derived isotopic labeling into acetyl-CoA, linking MPC2 to mitochondrial pyruvate import and downstream acetyl-CoA synthesis [#0, #1].\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1470400","name":null,"product":"mitochondrial pyruvate carrier protein 2, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1333600","name":null,"product":"mitochondrial pyruvate carrier protein 2, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1210600","name":null,"product":"mitochondrial pyruvate carrier protein 2, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"MPC2","evaluation":null}