{"gene":"PF3D7_0829200","run_date":"2026-09-08T12:51:27","timeline":{"discoveries":[{"year":2023,"finding":"PfPHB1 (PF3D7_0829200) localizes to the mitochondrion of P. falciparum asexual and sexual blood stages, as demonstrated by immunostaining showing branched mitochondrial structures, and was further validated as a mitochondrial organellar protein by fractionation/localization studies.","method":"Immunostaining, subcellular fractionation/localization validation","journal":"Biochemical pharmacology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct localization experiment with immunostaining and organellar validation, single lab, two orthogonal approaches","pmids":["37088154"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":"3D7"}]},{"year":2023,"finding":"PfPHB1 (PF3D7_0829200) physically interacts with PfPHB2 within P. falciparum mitochondria, as demonstrated by co-immunoprecipitation/interaction studies.","method":"Co-immunoprecipitation / protein interaction assay in parasite","journal":"Biochemical pharmacology","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — single Co-IP/interaction assay, single lab, corroborated by yeast two-hybrid in a separate study","pmids":["37088154","32883936"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2020,"finding":"PfPHB1 (PF3D7_0829200) interacts with PfPHB2 as shown by yeast two-hybrid analysis, suggesting they form heterodimeric supercomplexes analogous to canonical PHB1-PHB2 complexes in the mitochondrial inner membrane.","method":"Yeast two-hybrid analysis; homology modelling","journal":"Indian journal of medical microbiology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, single method (yeast two-hybrid), no in-parasite biochemical validation in this study","pmids":["32883936"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2023,"finding":"PfPHB1 (PF3D7_0829200) functionally complements yeast PHB1 mutants in S. cerevisiae, where it stabilizes mitochondrial DNA, maintains mitochondrial integrity, and rescues cell growth, demonstrating conserved mitochondrial function.","method":"Heterologous functional complementation in Saccharomyces cerevisiae PHB1 deletion mutants","journal":"Biochemical pharmacology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — functional complementation assay with multiple phenotypic readouts (mtDNA stability, mitochondrial integrity, growth rescue), single lab","pmids":["37088154"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":"3D7"}]},{"year":2023,"finding":"Rocaglamide (Roc-A), a known PHB inhibitor, inhibits growth of yeast cells complemented with PfPHB1 (PF3D7_0829200), validating PfPHB1 as a molecular target of Roc-A and contributing to Roc-A's nanomolar-range inhibition of P. falciparum asexual and sexual (gametocyte, oocyst) stages.","method":"Pharmacological inhibition of yeast complementation strains expressing PfPHB1; P. falciparum growth assay with Roc-A","journal":"Biochemical pharmacology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — orthogonal yeast complementation + parasite growth inhibition assays, single lab, multiple parasite strains tested","pmids":["37088154"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":"3D7"}]},{"year":2018,"finding":"Prohibitin 1 (the conserved PHB1 ortholog) localizes to the P. berghei mitochondrion (along with prohibitin 2 and stomatin-like protein), and could not be deleted from the Plasmodium genome, indicating it is essential for blood-stage parasite survival.","method":"Fluorescence microscopy (mitochondrial localization); attempted gene deletion (unsuccessful)","journal":"Cell reports","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct mitochondrial localization by fluorescence microscopy and failed deletion indicating essentiality, single lab, single species","pmids":["29669282"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2026,"finding":"PHB1 (PF3D7_0829200) is one of four SPFH proteins in P. falciparum that all localize to the parasite mitochondrion, as confirmed by epitope-tagging and localization studies in this comparative study of SPFH family members.","method":"Epitope tagging and fluorescence microscopy (comparative SPFH localization study)","journal":"PLoS pathogens","confidence":"Low","confidence_rationale":"Tier 3 / Weak — localization of PHB1 mentioned as part of a broader SPFH family study focused on STOML; specific functional data for PHB1 not provided beyond mitochondrial localization","pmids":["41662436"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PfPHB1 (PF3D7_0829200) is an essential mitochondrial inner-membrane protein in Plasmodium that localizes to the branched mitochondrial network in asexual and sexual blood stages, physically interacts with PfPHB2 to form heterodimeric complexes, stabilizes mitochondrial DNA and maintains mitochondrial integrity (as shown by functional complementation in yeast), and is a druggable target whose inhibition by Rocaglamide blocks parasite growth across drug-sensitive and drug-resistant strains as well as gametocyte and oocyst development."},"narrative":{"mechanistic_narrative":"PHB1 (PF3D7_0829200) is an essential mitochondrial protein of Plasmodium that localizes to the branched mitochondrial network of P. falciparum asexual and sexual blood stages [PMID:37088154]. Within the parasite mitochondrion it physically associates with PfPHB2, forming heterodimeric prohibitin complexes analogous to canonical inner-membrane PHB1–PHB2 assemblies [PMID:37088154, PMID:32883936]. Its mitochondrial function is conserved: PHB1 rescues S. cerevisiae PHB1-deletion mutants, restoring mitochondrial DNA stability, mitochondrial integrity, and cell growth [PMID:37088154]. In P. berghei the ortholog is refractory to genomic deletion, indicating that prohibitin function is required for blood-stage survival [PMID:29669282]. PHB1 is the molecular target of the PHB inhibitor Rocaglamide, which suppresses growth of yeast strains complemented with PHB1 and inhibits P. falciparum asexual, gametocyte, and oocyst stages at nanomolar concentrations, marking PHB1 as a druggable antimalarial target [PMID:37088154]. Beyond these observations, the precise biochemical role of PHB1 in maintaining the mitochondrial inner membrane has not been characterized in the available corpus.","teleology":[{"year":2018,"claim":"Establishing whether the Plasmodium prohibitin 1 ortholog is essential addressed whether it could serve as a viable drug target rather than a dispensable mitochondrial passenger.","evidence":"Fluorescence microscopy and attempted (unsuccessful) gene deletion in P. berghei","pmids":["29669282"],"confidence":"Medium","gaps":["Essentiality shown in P. berghei, not directly in P. falciparum PHB1","Failed deletion does not reveal which mitochondrial function is required","No conditional knockdown to define the essential process"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2020,"claim":"Testing whether PHB1 partners with PHB2 addressed whether the parasite builds heterodimeric prohibitin complexes like canonical eukaryotes.","evidence":"Yeast two-hybrid analysis with homology modelling","pmids":["32883936"],"confidence":"Low","gaps":["Single method (yeast two-hybrid) with no in-parasite biochemical validation in this study","Supercomplex stoichiometry inferred from homology, not measured","No structure of the parasite complex"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2023,"claim":"Determining PHB1's subcellular location and its physical interaction with PfPHB2 in parasites confirmed it is a bona fide mitochondrial prohibitin acting in a complex, not an isolated protein.","evidence":"Immunostaining, subcellular fractionation, and co-immunoprecipitation in P. falciparum 3D7","pmids":["37088154","32883936"],"confidence":"Medium","gaps":["Co-IP does not resolve direct versus indirect contact or complex architecture","Other complex members not identified","Interaction not mapped to specific domains"],"attribution":[{"species":"Plasmodium falciparum","strain":"3D7"}]},{"year":2023,"claim":"Heterologous complementation established that PHB1 carries out a conserved mitochondrial function, defining its cellular role in mtDNA stability and organellar integrity.","evidence":"Functional complementation of S. cerevisiae PHB1-deletion mutants with multiple phenotypic readouts","pmids":["37088154"],"confidence":"Medium","gaps":["Function inferred from yeast rescue, not directly demonstrated in the parasite","Biochemical mechanism of mtDNA stabilization unresolved","Native substrates or client proteins unidentified"],"attribution":[{"species":"Plasmodium falciparum","strain":"3D7"}]},{"year":2023,"claim":"Identifying PHB1 as the molecular target of Rocaglamide connected the mitochondrial protein to a chemically tractable, transmission-blocking antimalarial strategy.","evidence":"Rocaglamide inhibition of PHB1-complemented yeast plus P. falciparum growth assays across asexual, gametocyte, and oocyst stages","pmids":["37088154"],"confidence":"Medium","gaps":["Direct binding of Rocaglamide to parasite PHB1 not demonstrated biochemically","Whether Roc-A engages the PHB1–PHB2 complex or PHB1 alone unclear","Resistance mechanisms and target selectivity not defined"],"attribution":[{"species":"Plasmodium falciparum","strain":"3D7"}]},{"year":2026,"claim":"Placing PHB1 among the four mitochondrial SPFH proteins situated it within a broader membrane-scaffold family sharing the organelle.","evidence":"Epitope tagging and fluorescence microscopy in a comparative SPFH family study","pmids":["41662436"],"confidence":"Low","gaps":["PHB1-specific functional data not provided beyond mitochondrial localization","Functional relationship among the SPFH proteins not established for PHB1","Study focus was on a different SPFH member"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"The direct in-parasite biochemical function of PHB1 — its native complex architecture, molecular substrates, and mechanism of maintaining mitochondrial DNA and membrane integrity — remains undefined.","evidence":"","pmids":[],"confidence":"Low","gaps":["No structural model of the parasite PHB1–PHB2 complex","No direct demonstration of mtDNA/integrity function in the parasite itself","Direct Rocaglamide–PHB1 binding not shown"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["PHB1–PHB2 heterodimeric prohibitin complex"],"partners":["PFPHB2"],"other_free_text":["Essential for Plasmodium blood-stage survival (P. berghei ortholog non-deletable)","Molecular target of the antimalarial PHB inhibitor Rocaglamide, active against asexual, gametocyte, and oocyst stages","Member of the P. falciparum mitochondrial SPFH protein family"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"29669282","id":"PMC_29669282","title":"An Unusual Prohibitin Regulates Malaria Parasite Mitochondrial Membrane Potential.","date":"2018","source":"Cell reports","url":"https://pubmed.ncbi.nlm.nih.gov/29669282","citation_count":28,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["prohibitin 1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"37088154","id":"PMC_37088154","title":"Characterization of Plasmodium falciparum prohibitins as novel targets to block infection in humans by impairing the growth and transmission of the parasite.","date":"2023","source":"Biochemical pharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/37088154","citation_count":9,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PHB1","PfPHB1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"32883936","id":"PMC_32883936","title":"Functional studies of Plasmodium falciparum's prohibitin1 and prohibitin 2 in yeast.","date":"2020","source":"Indian journal of medical microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/32883936","citation_count":7,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PHB1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"40669099","id":"PMC_40669099","title":"Development of a multi-epitope vaccine candidate targeting blood-stage of malaria through immunoinformatics approach.","date":"2025","source":"Human immunology","url":"https://pubmed.ncbi.nlm.nih.gov/40669099","citation_count":3,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PfPHB1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"41662436","id":"PMC_41662436","title":"Plasmodium falciparum stomatin-like protein forms a putative complex with a metalloprotease in distinct mitochondrial loci.","date":"2026","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/41662436","citation_count":1,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["prohibitin 1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":5350,"output_tokens":1813,"usd":0.021622,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6939,"output_tokens":2746,"usd":0.051673,"stage2_stop_reason":"end_turn"},"total_usd":0.073295,"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\": 2023,\n      \"finding\": \"PfPHB1 (PF3D7_0829200) localizes to the mitochondrion of P. falciparum asexual and sexual blood stages, as demonstrated by immunostaining showing branched mitochondrial structures, and was further validated as a mitochondrial organellar protein by fractionation/localization studies.\",\n      \"method\": \"Immunostaining, subcellular fractionation/localization validation\",\n      \"journal\": \"Biochemical pharmacology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct localization experiment with immunostaining and organellar validation, single lab, two orthogonal approaches\",\n      \"pmids\": [\"37088154\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"3D7\"}]\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"PfPHB1 (PF3D7_0829200) physically interacts with PfPHB2 within P. falciparum mitochondria, as demonstrated by co-immunoprecipitation/interaction studies.\",\n      \"method\": \"Co-immunoprecipitation / protein interaction assay in parasite\",\n      \"journal\": \"Biochemical pharmacology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — single Co-IP/interaction assay, single lab, corroborated by yeast two-hybrid in a separate study\",\n      \"pmids\": [\"37088154\", \"32883936\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"PfPHB1 (PF3D7_0829200) interacts with PfPHB2 as shown by yeast two-hybrid analysis, suggesting they form heterodimeric supercomplexes analogous to canonical PHB1-PHB2 complexes in the mitochondrial inner membrane.\",\n      \"method\": \"Yeast two-hybrid analysis; homology modelling\",\n      \"journal\": \"Indian journal of medical microbiology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, single method (yeast two-hybrid), no in-parasite biochemical validation in this study\",\n      \"pmids\": [\"32883936\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"PfPHB1 (PF3D7_0829200) functionally complements yeast PHB1 mutants in S. cerevisiae, where it stabilizes mitochondrial DNA, maintains mitochondrial integrity, and rescues cell growth, demonstrating conserved mitochondrial function.\",\n      \"method\": \"Heterologous functional complementation in Saccharomyces cerevisiae PHB1 deletion mutants\",\n      \"journal\": \"Biochemical pharmacology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — functional complementation assay with multiple phenotypic readouts (mtDNA stability, mitochondrial integrity, growth rescue), single lab\",\n      \"pmids\": [\"37088154\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"3D7\"}]\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"Rocaglamide (Roc-A), a known PHB inhibitor, inhibits growth of yeast cells complemented with PfPHB1 (PF3D7_0829200), validating PfPHB1 as a molecular target of Roc-A and contributing to Roc-A's nanomolar-range inhibition of P. falciparum asexual and sexual (gametocyte, oocyst) stages.\",\n      \"method\": \"Pharmacological inhibition of yeast complementation strains expressing PfPHB1; P. falciparum growth assay with Roc-A\",\n      \"journal\": \"Biochemical pharmacology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — orthogonal yeast complementation + parasite growth inhibition assays, single lab, multiple parasite strains tested\",\n      \"pmids\": [\"37088154\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"3D7\"}]\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"Prohibitin 1 (the conserved PHB1 ortholog) localizes to the P. berghei mitochondrion (along with prohibitin 2 and stomatin-like protein), and could not be deleted from the Plasmodium genome, indicating it is essential for blood-stage parasite survival.\",\n      \"method\": \"Fluorescence microscopy (mitochondrial localization); attempted gene deletion (unsuccessful)\",\n      \"journal\": \"Cell reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct mitochondrial localization by fluorescence microscopy and failed deletion indicating essentiality, single lab, single species\",\n      \"pmids\": [\"29669282\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"PHB1 (PF3D7_0829200) is one of four SPFH proteins in P. falciparum that all localize to the parasite mitochondrion, as confirmed by epitope-tagging and localization studies in this comparative study of SPFH family members.\",\n      \"method\": \"Epitope tagging and fluorescence microscopy (comparative SPFH localization study)\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — localization of PHB1 mentioned as part of a broader SPFH family study focused on STOML; specific functional data for PHB1 not provided beyond mitochondrial localization\",\n      \"pmids\": [\"41662436\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"PfPHB1 (PF3D7_0829200) is an essential mitochondrial inner-membrane protein in Plasmodium that localizes to the branched mitochondrial network in asexual and sexual blood stages, physically interacts with PfPHB2 to form heterodimeric complexes, stabilizes mitochondrial DNA and maintains mitochondrial integrity (as shown by functional complementation in yeast), and is a druggable target whose inhibition by Rocaglamide blocks parasite growth across drug-sensitive and drug-resistant strains as well as gametocyte and oocyst development.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PHB1 (PF3D7_0829200) is an essential mitochondrial protein of Plasmodium that localizes to the branched mitochondrial network of P. falciparum asexual and sexual blood stages [#0]. Within the parasite mitochondrion it physically associates with PfPHB2, forming heterodimeric prohibitin complexes analogous to canonical inner-membrane PHB1–PHB2 assemblies [#1]. Its mitochondrial function is conserved: PHB1 rescues S. cerevisiae PHB1-deletion mutants, restoring mitochondrial DNA stability, mitochondrial integrity, and cell growth [#3]. In P. berghei the ortholog is refractory to genomic deletion, indicating that prohibitin function is required for blood-stage survival [#5]. PHB1 is the molecular target of the PHB inhibitor Rocaglamide, which suppresses growth of yeast strains complemented with PHB1 and inhibits P. falciparum asexual, gametocyte, and oocyst stages at nanomolar concentrations, marking PHB1 as a druggable antimalarial target [#4]. Beyond these observations, the precise biochemical role of PHB1 in maintaining the mitochondrial inner membrane has not been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2018,\n      \"claim\": \"Establishing whether the Plasmodium prohibitin 1 ortholog is essential addressed whether it could serve as a viable drug target rather than a dispensable mitochondrial passenger.\",\n      \"evidence\": \"Fluorescence microscopy and attempted (unsuccessful) gene deletion in P. berghei\",\n      \"pmids\": [\"29669282\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Essentiality shown in P. berghei, not directly in P. falciparum PHB1\",\n        \"Failed deletion does not reveal which mitochondrial function is required\",\n        \"No conditional knockdown to define the essential process\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Testing whether PHB1 partners with PHB2 addressed whether the parasite builds heterodimeric prohibitin complexes like canonical eukaryotes.\",\n      \"evidence\": \"Yeast two-hybrid analysis with homology modelling\",\n      \"pmids\": [\"32883936\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Single method (yeast two-hybrid) with no in-parasite biochemical validation in this study\",\n        \"Supercomplex stoichiometry inferred from homology, not measured\",\n        \"No structure of the parasite complex\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Determining PHB1's subcellular location and its physical interaction with PfPHB2 in parasites confirmed it is a bona fide mitochondrial prohibitin acting in a complex, not an isolated protein.\",\n      \"evidence\": \"Immunostaining, subcellular fractionation, and co-immunoprecipitation in P. falciparum 3D7\",\n      \"pmids\": [\"37088154\", \"32883936\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Co-IP does not resolve direct versus indirect contact or complex architecture\",\n        \"Other complex members not identified\",\n        \"Interaction not mapped to specific domains\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"3D7\"}]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Heterologous complementation established that PHB1 carries out a conserved mitochondrial function, defining its cellular role in mtDNA stability and organellar integrity.\",\n      \"evidence\": \"Functional complementation of S. cerevisiae PHB1-deletion mutants with multiple phenotypic readouts\",\n      \"pmids\": [\"37088154\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Function inferred from yeast rescue, not directly demonstrated in the parasite\",\n        \"Biochemical mechanism of mtDNA stabilization unresolved\",\n        \"Native substrates or client proteins unidentified\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"3D7\"}]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Identifying PHB1 as the molecular target of Rocaglamide connected the mitochondrial protein to a chemically tractable, transmission-blocking antimalarial strategy.\",\n      \"evidence\": \"Rocaglamide inhibition of PHB1-complemented yeast plus P. falciparum growth assays across asexual, gametocyte, and oocyst stages\",\n      \"pmids\": [\"37088154\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Direct binding of Rocaglamide to parasite PHB1 not demonstrated biochemically\",\n        \"Whether Roc-A engages the PHB1–PHB2 complex or PHB1 alone unclear\",\n        \"Resistance mechanisms and target selectivity not defined\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"3D7\"}]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"Placing PHB1 among the four mitochondrial SPFH proteins situated it within a broader membrane-scaffold family sharing the organelle.\",\n      \"evidence\": \"Epitope tagging and fluorescence microscopy in a comparative SPFH family study\",\n      \"pmids\": [\"41662436\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"PHB1-specific functional data not provided beyond mitochondrial localization\",\n        \"Functional relationship among the SPFH proteins not established for PHB1\",\n        \"Study focus was on a different SPFH member\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The direct in-parasite biochemical function of PHB1 — its native complex architecture, molecular substrates, and mechanism of maintaining mitochondrial DNA and membrane integrity — remains undefined.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No structural model of the parasite PHB1–PHB2 complex\",\n        \"No direct demonstration of mtDNA/integrity function in the parasite itself\",\n        \"Direct Rocaglamide–PHB1 binding not shown\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0042803\", \"supporting_discovery_ids\": [1, 2]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005739\", \"supporting_discovery_ids\": [0, 5, 6]},\n      {\"term_id\": \"GO:0005743\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0007005\", \"supporting_discovery_ids\": [3]},\n      {\"term_id\": \"GO:0033955\", \"supporting_discovery_ids\": [3]}\n    ],\n    \"complexes\": [\n      \"PHB1–PHB2 heterodimeric prohibitin complex\"\n    ],\n    \"partners\": [\n      \"PfPHB2\"\n    ],\n    \"other_free_text\": [\n      \"Essential for Plasmodium blood-stage survival (P. berghei ortholog non-deletable)\",\n      \"Molecular target of the antimalarial PHB inhibitor Rocaglamide, active against asexual, gametocyte, and oocyst stages\",\n      \"Member of the P. falciparum mitochondrial SPFH protein family\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0829200","name":null,"product":"prohibitin 1","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0701500","name":null,"product":"prohibitin 1","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1323400","name":null,"product":"prohibitin 1, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"PHB1","evaluation":null}