{"gene":"PF3D7_0705900","run_date":"2026-09-08T12:51:27","timeline":{"discoveries":[{"year":2011,"finding":"PF3D7_0705900 (ATP synthase subunit C, a canonical ATP synthase subunit) localizes to the mitochondrion of P. falciparum blood stages. Epitope-tagged versions of seven canonical ATP synthase subunits, including subunit C, were expressed in transgenic P. falciparum lines; all but one localized to the mitochondrion. Blue native gel electrophoresis of P. falciparum mitochondrial membranes indicated the ATP synthase complex has a molecular mass greater than 1 million daltons, consistent with dimeric assembly, suggesting additional unknown subunits beyond the canonical ones. Attempts to genetically disrupt the β and γ subunit genes were unsuccessful, implying the complex (and by extension its subunits) is essential in blood stages.","method":"Epitope-tagging of subunits in transgenic P. falciparum, immunofluorescence localization, blue native gel electrophoresis of mitochondrial membranes, attempted gene disruption","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal immunological and native-gel approaches in a single lab; mitochondrial localization established by direct imaging, and dimeric complex assembly by native PAGE, but subunit C specifically is one of seven subunits examined without individual functional dissection","pmids":["21984828"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2009,"finding":"Computational and structural fingerprint analysis identified a candidate for the ATP synthase subunit a (and subunit b) in Plasmodium spp. The transmembrane helix IV of the Plasmodium ATP synthase subunit a candidate lacks an essential Arg residue found in canonical subunit a, indicating divergence from orthologs. These membrane anchor subunits of the F(o) sector are highly divergent from canonical orthologs and were proposed as promising drug targets. (Note: PF3D7_0705900 is annotated as subunit C; this paper addresses subunit a/b candidates and touches on the broader F(o) subunit landscape, including the context in which subunit C operates.)","method":"Bioinformatic/structural fingerprint analysis and integration of proteomics data from other protists to identify divergent membrane anchor subunits in Plasmodium","journal":"Mitochondrion","confidence":"Low","confidence_rationale":"Tier 4 / Weak — computational prediction only, no direct biochemical or genetic experiment performed on PF3D7_0705900 specifically","pmids":["19682605"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2015,"finding":"Genetic knockout of the ATP synthase β subunit in P. berghei showed the ATP synthase complex is dispensable for asexual blood-stage growth but essential for mosquito-stage viability; ookinetes lacking the β subunit had normal motility but could not survive in the mosquito midgut and never produced oocysts or sporozoites. Crossing the β-subunit knockout with a male-deficient strain restored oocyst and sporozoite production, demonstrating that ATP synthase is essential through the female, mitochondrion-carrying line of sexual reproduction. This establishes the essentiality of the ATP synthase complex (of which subunit C is a member) during the mosquito phase.","method":"Gene knockout of ATP synthase β subunit in P. berghei, mosquito transmission assays, genetic complementation cross with male-deficient strain","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean KO with defined phenotypic readouts and genetic complementation, but finding pertains to the β subunit specifically and attributes to the complex as a whole; subunit C (PF3D7_0705900) is a member of the same complex but was not individually manipulated","pmids":["25831536"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2024,"finding":"Mitochondrial ATP synthesis (the function of the ATP synthase complex, which includes subunit C) is essential for completion of male gametogenesis in P. falciparum. Using a genetically encoded ratiometric ATP sensor, gametocytes were shown to maintain cytoplasmic ATP homeostasis in the absence of mitochondrial respiration, indicating the mitochondrion's essentiality is specific to transmission-stage processes rather than general ATP supply. The male gametocyte mitochondrion was shown to be less active than the female mitochondrion and more sensitive to antimalarials targeting mitochondrial energy metabolism.","method":"Sex-specific antibody labeling, functional mitochondrial dye labeling, genetically encoded ratiometric ATP sensor, pharmacological inhibition of mitochondrial ATP synthesis","journal":"Communications biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple orthogonal methods (genetic sensor, functional labeling, pharmacology) in a single lab; establishes the functional role of the ATP synthase complex in gametogenesis but does not individually manipulate subunit C","pmids":["39550509"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PF3D7_0705900 (ATP synthase subunit C, putative) localizes to the P. falciparum mitochondrion as part of a large (>1 MDa) dimeric ATP synthase complex; the complex as a whole is refractory to genetic disruption in blood-stage P. falciparum and is essential for mosquito-stage viability and male gametogenesis, but no experiment has directly and individually manipulated subunit C itself to assign it a specific catalytic or structural function distinct from the broader complex."},"narrative":{"mechanistic_narrative":"PF3D7_0705900 is annotated as a putative ATP synthase subunit C of Plasmodium falciparum, and the available evidence characterizes it only as a component of the mitochondrial ATP synthase complex rather than as an individually dissected protein. An epitope-tagged version of subunit C localizes to the mitochondrion of blood-stage P. falciparum, and blue native gel electrophoresis places the assembled ATP synthase at greater than 1 MDa, consistent with a dimeric complex that likely contains additional non-canonical subunits [PMID:21984828]. Functional and genetic manipulation has been performed only on other subunits of the same complex: the β and γ subunit genes resisted disruption in blood-stage P. falciparum, implying essentiality of the complex [PMID:21984828], and in P. berghei the β-subunit is dispensable for asexual blood-stage growth but essential for mosquito-stage viability through the female, mitochondrion-carrying line [PMID:25831536]. In P. falciparum, mitochondrial ATP synthesis by this complex is required for completion of male gametogenesis, a transmission-stage role distinct from bulk cytoplasmic ATP supply [PMID:39550509]. No experiment in the available corpus has individually manipulated subunit C to assign it a catalytic or structural function separate from the complex; beyond its mitochondrial localization and complex membership [PMID:21984828], subunit C itself remains uncharacterized.","teleology":[{"year":2009,"claim":"Before direct study, the composition of the Plasmodium F(o) sector was uncertain; bioinformatic fingerprinting of membrane-anchor candidates began mapping the divergent F(o) subunit landscape in which subunit C operates.","evidence":"Computational/structural fingerprint analysis integrating proteomics from other protists to identify divergent subunit a/b candidates in Plasmodium","pmids":["19682605"],"confidence":"Low","gaps":["Purely computational; no biochemical or genetic experiment on PF3D7_0705900","Addresses subunit a/b candidates, not subunit C directly","Divergence of subunit C itself not assessed"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2011,"claim":"It was unknown where subunit C resides and how the complex assembles; tagging and native-gel analysis placed subunit C in the mitochondrion within a >1 MDa dimeric ATP synthase and indicated the complex is essential in blood stages.","evidence":"Epitope-tagging of seven canonical subunits in transgenic P. falciparum, immunofluorescence, blue native PAGE of mitochondrial membranes, and attempted disruption of β/γ subunits","pmids":["21984828"],"confidence":"Medium","gaps":["Subunit C examined as one of seven subunits, not functionally dissected","Essentiality inferred from β/γ disruption failure, not from subunit C itself","Additional non-canonical subunits implied by mass but not identified"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2015,"claim":"Whether the ATP synthase complex is required across the life cycle was unresolved; β-subunit knockout in P. berghei showed the complex is dispensable for asexual blood-stage growth but essential for mosquito-stage viability through the female lineage.","evidence":"β-subunit gene knockout in P. berghei, mosquito transmission assays, and complementation cross with a male-deficient strain","pmids":["25831536"],"confidence":"Medium","gaps":["Phenotype attributed to β subunit, not subunit C","Shown in P. berghei, not P. falciparum","Does not establish whether subunit C is required for these stages"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2024,"claim":"The stage-specific function of the complex needed clarification; mitochondrial ATP synthesis was shown to be essential for male gametogenesis in P. falciparum, distinct from general cytoplasmic ATP supply.","evidence":"Sex-specific labeling, mitochondrial dye labeling, a genetically encoded ratiometric ATP sensor, and pharmacological inhibition of mitochondrial ATP synthesis in P. falciparum gametocytes","pmids":["39550509"],"confidence":"Medium","gaps":["Function attributed to the complex, not subunit C individually","Mechanism linking ATP synthesis to gametogenesis not defined","No manipulation of subunit C to test its contribution"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"It remains unknown what specific catalytic or structural role subunit C (PF3D7_0705900) plays, since no experiment has individually manipulated the subunit apart from the broader ATP synthase complex.","evidence":"No direct genetic or biochemical dissection of PF3D7_0705900 in the available corpus","pmids":[],"confidence":"Low","gaps":["No individual knockout/knockdown of subunit C","No structural placement within the assembled complex","No assay of subunit C contribution to catalysis or dimerization"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["Mitochondrial ATP synthase complex (>1 MDa, dimeric)"],"partners":["ATP SYNTHASE Β SUBUNIT (SAME COMPLEX)","ATP SYNTHASE Γ SUBUNIT (SAME COMPLEX)"],"other_free_text":["Characterized only as a member of the P. falciparum mitochondrial ATP synthase complex; no individual functional manipulation of subunit C exists in the corpus.","Complex essentiality established for blood-stage (via β/γ in P. falciparum) and mosquito-stage/male gametogenesis (via β in P. berghei and pharmacology in P. falciparum), not via subunit C directly."]}},"prefetch_data":{},"corpus_meta":[{"pmid":"19575561","id":"PMC_19575561","title":"Mitochondrial evolution and functions in malaria parasites.","date":"2009","source":"Annual review of microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/19575561","citation_count":181,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ATP"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"25831536","id":"PMC_25831536","title":"Mitochondrial ATP synthase is dispensable in blood-stage Plasmodium berghei rodent malaria but essential in the mosquito phase.","date":"2015","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/25831536","citation_count":88,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ATP"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"11803022","id":"PMC_11803022","title":"Role of complex II in anaerobic respiration of the parasite mitochondria from Ascaris suum and Plasmodium falciparum.","date":"2002","source":"Biochimica et biophysica acta","url":"https://pubmed.ncbi.nlm.nih.gov/11803022","citation_count":84,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ATP"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"15552397","id":"PMC_15552397","title":"The multiple roles of the mitochondrion of the malarial parasite.","date":"2004","source":"Parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/15552397","citation_count":66,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ATP"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"25823686","id":"PMC_25823686","title":"Triaminopyrimidine is a fast-killing and long-acting antimalarial clinical candidate.","date":"2015","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/25823686","citation_count":59,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ATP"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"29215331","id":"PMC_29215331","title":"A comparative transcriptomic analysis of replicating and dormant liver stages of the relapsing malaria parasite Plasmodium cynomolgi.","date":"2017","source":"eLife","url":"https://pubmed.ncbi.nlm.nih.gov/29215331","citation_count":57,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ATP"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"21984828","id":"PMC_21984828","title":"ATP synthase complex of Plasmodium falciparum: dimeric assembly in mitochondrial membranes and resistance to genetic disruption.","date":"2011","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/21984828","citation_count":54,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ATP"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"2226706","id":"PMC_2226706","title":"Plasmodium falciparum: ATP/ADP transport across the parasitophorous vacuolar and plasma membranes.","date":"1990","source":"Experimental parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/2226706","citation_count":41,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ATP"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"19682605","id":"PMC_19682605","title":"Identification of mitochondrial Complex II subunits SDH3 and SDH4 and ATP synthase subunits a and b in Plasmodium spp.","date":"2009","source":"Mitochondrion","url":"https://pubmed.ncbi.nlm.nih.gov/19682605","citation_count":27,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ATP"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"39550509","id":"PMC_39550509","title":"Mitochondrial ATP synthesis is essential for efficient gametogenesis in Plasmodium falciparum.","date":"2024","source":"Communications biology","url":"https://pubmed.ncbi.nlm.nih.gov/39550509","citation_count":10,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ATP"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":6766,"output_tokens":1591,"usd":0.022082,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6657,"output_tokens":2573,"usd":0.048805,"stage2_stop_reason":"end_turn"},"total_usd":0.070887,"stage1_batch_id":"msgbatch_01DisAaTypwmC8QwdMBuePHo","stage2_batch_id":"msgbatch_0184zxZTqxiEfdYYfPMfkqjb","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2011,\n      \"finding\": \"PF3D7_0705900 (ATP synthase subunit C, a canonical ATP synthase subunit) localizes to the mitochondrion of P. falciparum blood stages. Epitope-tagged versions of seven canonical ATP synthase subunits, including subunit C, were expressed in transgenic P. falciparum lines; all but one localized to the mitochondrion. Blue native gel electrophoresis of P. falciparum mitochondrial membranes indicated the ATP synthase complex has a molecular mass greater than 1 million daltons, consistent with dimeric assembly, suggesting additional unknown subunits beyond the canonical ones. Attempts to genetically disrupt the β and γ subunit genes were unsuccessful, implying the complex (and by extension its subunits) is essential in blood stages.\",\n      \"method\": \"Epitope-tagging of subunits in transgenic P. falciparum, immunofluorescence localization, blue native gel electrophoresis of mitochondrial membranes, attempted gene disruption\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal immunological and native-gel approaches in a single lab; mitochondrial localization established by direct imaging, and dimeric complex assembly by native PAGE, but subunit C specifically is one of seven subunits examined without individual functional dissection\",\n      \"pmids\": [\"21984828\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"Computational and structural fingerprint analysis identified a candidate for the ATP synthase subunit a (and subunit b) in Plasmodium spp. The transmembrane helix IV of the Plasmodium ATP synthase subunit a candidate lacks an essential Arg residue found in canonical subunit a, indicating divergence from orthologs. These membrane anchor subunits of the F(o) sector are highly divergent from canonical orthologs and were proposed as promising drug targets. (Note: PF3D7_0705900 is annotated as subunit C; this paper addresses subunit a/b candidates and touches on the broader F(o) subunit landscape, including the context in which subunit C operates.)\",\n      \"method\": \"Bioinformatic/structural fingerprint analysis and integration of proteomics data from other protists to identify divergent membrane anchor subunits in Plasmodium\",\n      \"journal\": \"Mitochondrion\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 4 / Weak — computational prediction only, no direct biochemical or genetic experiment performed on PF3D7_0705900 specifically\",\n      \"pmids\": [\"19682605\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"Genetic knockout of the ATP synthase β subunit in P. berghei showed the ATP synthase complex is dispensable for asexual blood-stage growth but essential for mosquito-stage viability; ookinetes lacking the β subunit had normal motility but could not survive in the mosquito midgut and never produced oocysts or sporozoites. Crossing the β-subunit knockout with a male-deficient strain restored oocyst and sporozoite production, demonstrating that ATP synthase is essential through the female, mitochondrion-carrying line of sexual reproduction. This establishes the essentiality of the ATP synthase complex (of which subunit C is a member) during the mosquito phase.\",\n      \"method\": \"Gene knockout of ATP synthase β subunit in P. berghei, mosquito transmission assays, genetic complementation cross with male-deficient strain\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean KO with defined phenotypic readouts and genetic complementation, but finding pertains to the β subunit specifically and attributes to the complex as a whole; subunit C (PF3D7_0705900) is a member of the same complex but was not individually manipulated\",\n      \"pmids\": [\"25831536\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"Mitochondrial ATP synthesis (the function of the ATP synthase complex, which includes subunit C) is essential for completion of male gametogenesis in P. falciparum. Using a genetically encoded ratiometric ATP sensor, gametocytes were shown to maintain cytoplasmic ATP homeostasis in the absence of mitochondrial respiration, indicating the mitochondrion's essentiality is specific to transmission-stage processes rather than general ATP supply. The male gametocyte mitochondrion was shown to be less active than the female mitochondrion and more sensitive to antimalarials targeting mitochondrial energy metabolism.\",\n      \"method\": \"Sex-specific antibody labeling, functional mitochondrial dye labeling, genetically encoded ratiometric ATP sensor, pharmacological inhibition of mitochondrial ATP synthesis\",\n      \"journal\": \"Communications biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple orthogonal methods (genetic sensor, functional labeling, pharmacology) in a single lab; establishes the functional role of the ATP synthase complex in gametogenesis but does not individually manipulate subunit C\",\n      \"pmids\": [\"39550509\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"PF3D7_0705900 (ATP synthase subunit C, putative) localizes to the P. falciparum mitochondrion as part of a large (>1 MDa) dimeric ATP synthase complex; the complex as a whole is refractory to genetic disruption in blood-stage P. falciparum and is essential for mosquito-stage viability and male gametogenesis, but no experiment has directly and individually manipulated subunit C itself to assign it a specific catalytic or structural function distinct from the broader complex.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_0705900 is annotated as a putative ATP synthase subunit C of Plasmodium falciparum, and the available evidence characterizes it only as a component of the mitochondrial ATP synthase complex rather than as an individually dissected protein. An epitope-tagged version of subunit C localizes to the mitochondrion of blood-stage P. falciparum, and blue native gel electrophoresis places the assembled ATP synthase at greater than 1 MDa, consistent with a dimeric complex that likely contains additional non-canonical subunits [#0]. Functional and genetic manipulation has been performed only on other subunits of the same complex: the \\u03b2 and \\u03b3 subunit genes resisted disruption in blood-stage P. falciparum, implying essentiality of the complex [#0], and in P. berghei the \\u03b2-subunit is dispensable for asexual blood-stage growth but essential for mosquito-stage viability through the female, mitochondrion-carrying line [#2]. In P. falciparum, mitochondrial ATP synthesis by this complex is required for completion of male gametogenesis, a transmission-stage role distinct from bulk cytoplasmic ATP supply [#3]. No experiment in the available corpus has individually manipulated subunit C to assign it a catalytic or structural function separate from the complex; beyond its mitochondrial localization and complex membership [#0], subunit C itself remains uncharacterized.\",\n  \"teleology\": [\n    {\n      \"year\": 2009,\n      \"claim\": \"Before direct study, the composition of the Plasmodium F(o) sector was uncertain; bioinformatic fingerprinting of membrane-anchor candidates began mapping the divergent F(o) subunit landscape in which subunit C operates.\",\n      \"evidence\": \"Computational/structural fingerprint analysis integrating proteomics from other protists to identify divergent subunit a/b candidates in Plasmodium\",\n      \"pmids\": [\n        \"19682605\"\n      ],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Purely computational; no biochemical or genetic experiment on PF3D7_0705900\",\n        \"Addresses subunit a/b candidates, not subunit C directly\",\n        \"Divergence of subunit C itself not assessed\"\n      ],\n      \"attribution\": [\n        {\n          \"species\": \"Plasmodium falciparum\",\n          \"strain\": \"\"\n        }\n      ]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"It was unknown where subunit C resides and how the complex assembles; tagging and native-gel analysis placed subunit C in the mitochondrion within a >1 MDa dimeric ATP synthase and indicated the complex is essential in blood stages.\",\n      \"evidence\": \"Epitope-tagging of seven canonical subunits in transgenic P. falciparum, immunofluorescence, blue native PAGE of mitochondrial membranes, and attempted disruption of \\u03b2/\\u03b3 subunits\",\n      \"pmids\": [\n        \"21984828\"\n      ],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Subunit C examined as one of seven subunits, not functionally dissected\",\n        \"Essentiality inferred from \\u03b2/\\u03b3 disruption failure, not from subunit C itself\",\n        \"Additional non-canonical subunits implied by mass but not identified\"\n      ],\n      \"attribution\": [\n        {\n          \"species\": \"Plasmodium falciparum\",\n          \"strain\": \"\"\n        }\n      ]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Whether the ATP synthase complex is required across the life cycle was unresolved; \\u03b2-subunit knockout in P. berghei showed the complex is dispensable for asexual blood-stage growth but essential for mosquito-stage viability through the female lineage.\",\n      \"evidence\": \"\\u03b2-subunit gene knockout in P. berghei, mosquito transmission assays, and complementation cross with a male-deficient strain\",\n      \"pmids\": [\n        \"25831536\"\n      ],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Phenotype attributed to \\u03b2 subunit, not subunit C\",\n        \"Shown in P. berghei, not P. falciparum\",\n        \"Does not establish whether subunit C is required for these stages\"\n      ],\n      \"attribution\": [\n        {\n          \"species\": \"Plasmodium berghei\",\n          \"strain\": \"\"\n        }\n      ]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"The stage-specific function of the complex needed clarification; mitochondrial ATP synthesis was shown to be essential for male gametogenesis in P. falciparum, distinct from general cytoplasmic ATP supply.\",\n      \"evidence\": \"Sex-specific labeling, mitochondrial dye labeling, a genetically encoded ratiometric ATP sensor, and pharmacological inhibition of mitochondrial ATP synthesis in P. falciparum gametocytes\",\n      \"pmids\": [\n        \"39550509\"\n      ],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Function attributed to the complex, not subunit C individually\",\n        \"Mechanism linking ATP synthesis to gametogenesis not defined\",\n        \"No manipulation of subunit C to test its contribution\"\n      ],\n      \"attribution\": [\n        {\n          \"species\": \"Plasmodium falciparum\",\n          \"strain\": \"\"\n        }\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"It remains unknown what specific catalytic or structural role subunit C (PF3D7_0705900) plays, since no experiment has individually manipulated the subunit apart from the broader ATP synthase complex.\",\n      \"evidence\": \"No direct genetic or biochemical dissection of PF3D7_0705900 in the available corpus\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No individual knockout/knockdown of subunit C\",\n        \"No structural placement within the assembled complex\",\n        \"No assay of subunit C contribution to catalysis or dimerization\"\n      ],\n      \"attribution\": [\n        {\n          \"species\": \"Plasmodium falciparum\",\n          \"strain\": \"\"\n        }\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\n        \"term_id\": \"GO:0046933\",\n        \"supporting_discovery_ids\": [\n          0,\n          3\n        ]\n      }\n    ],\n    \"localization\": [\n      {\n        \"term_id\": \"GO:0005739\",\n        \"supporting_discovery_ids\": [\n          0\n        ]\n      }\n    ],\n    \"pathway\": [\n      {\n        \"term_id\": \"GO:0042776\",\n        \"supporting_discovery_ids\": [\n          0,\n          2,\n          3\n        ]\n      }\n    ],\n    \"complexes\": [\n      \"Mitochondrial ATP synthase complex (>1 MDa, dimeric)\"\n    ],\n    \"partners\": [\n      \"ATP synthase \\u03b2 subunit (same complex)\",\n      \"ATP synthase \\u03b3 subunit (same complex)\"\n    ],\n    \"other_free_text\": [\n      \"Characterized only as a member of the P. falciparum mitochondrial ATP synthase complex; no individual functional manipulation of subunit C exists in the corpus.\",\n      \"Complex essentiality established for blood-stage (via \\u03b2/\\u03b3 in P. falciparum) and mosquito-stage/male gametogenesis (via \\u03b2 in P. berghei and pharmacology in P. falciparum), not via subunit C directly.\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0705900","name":null,"product":"ATP synthase subunit C, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0803500","name":null,"product":"ATP synthase subunit C, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0104400","name":null,"product":"ATP synthase subunit C, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"","evaluation":null}