{"gene":"PF3D7_1004000","run_date":"2026-09-08T12:51:27","timeline":{"discoveries":[{"year":2018,"finding":"PF3D7_1004000 (PfmRPL13), a large mitoribosomal protein, localizes to the mitochondrion of P. falciparum, as determined by direct localization experiments.","method":"Subcellular localization assay (conditional knockdown system TetR-DOZI-aptamer, fluorescence-based localization)","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct localization experiment in P. falciparum with conditional knockdown, single lab, multiple phenotypic readouts","pmids":["29626096"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2018,"finding":"Conditional knockdown of PF3D7_1004000 (PfmRPL13) causes mitochondrial electron transport chain (mtETC) deficiency and loss of mitochondrial membrane potential (Δψm), establishing that L13 is essential for mitochondrial functional integrity in P. falciparum.","method":"Conditional knockdown (TetR-DOZI-aptamer system) with mtETC activity assay and mitochondrial membrane potential measurement","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 2 / Strong — conditional knockdown with multiple orthogonal functional readouts (mtETC deficiency, Δψm loss, parasite death, rescue with second copy) in a single rigorous study","pmids":["29626096"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2018,"finding":"Ablation of PF3D7_1004000 (PfmRPL13) results in an unusually elongated and branched mitochondrial morphology, demonstrating that L13 is required for normal mitochondrial structural integrity.","method":"Transmission electron microscopy of conditional knockdown parasites","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 2 / Strong — ultrastructural evidence by TEM combined with conditional knockdown, part of a multi-method study with functional validation","pmids":["29626096"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2018,"finding":"Knockdown of PF3D7_1004000 (PfmRPL13) renders P. falciparum hypersensitive to proguanil, consistent with L13's role in maintaining mitochondrial membrane potential through mitoribosome-dependent translation of mtETC subunits.","method":"Drug sensitivity assay on conditional knockdown parasites (TetR-DOZI-aptamer system)","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — drug sensitivity phenotype linked mechanistically to Δψm loss, single lab, single method for this specific finding","pmids":["29626096"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2018,"finding":"Growth arrest of PF3D7_1004000 (PfmRPL13) knockdown parasites was rescued by a second copy of PfmRPL13 but not by supplementation with decylubiquinone or addition of a yeast dihydroorotate dehydrogenase gene, indicating that L13's essential function is specifically tied to mitoribosomal translation rather than ubiquinol regeneration or pyrimidine biosynthesis.","method":"Genetic rescue experiment (complementation with second copy; supplementation controls) in conditional knockdown background","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 2 / Strong — epistasis-style rescue experiment with positive and negative controls, directly places L13 function in mitoribosomal translation pathway","pmids":["29626096"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PF3D7_1004000 (L13/PfmRPL13) is an essential large subunit mitoribosomal protein in P. falciparum that localizes to the mitochondrion and is required for mitoribosomal translation of mitochondrially-encoded electron transport chain subunits (cyt b, COXI, COXIII), thereby maintaining mtETC activity, mitochondrial membrane potential, and normal mitochondrial morphology; its loss causes mtETC deficiency, collapse of Δψm, aberrant elongated/branched mitochondrial structure, hypersensitivity to proguanil, and parasite death."},"narrative":{"mechanistic_narrative":"PF3D7_1004000 (L13) is an essential large mitoribosomal protein of Plasmodium falciparum that localizes to the mitochondrion and is required for mitochondrial functional and structural integrity [PMID:29626096]. Conditional knockdown of L13 causes electron transport chain deficiency and collapse of the mitochondrial membrane potential [PMID:29626096], produces an aberrant elongated and branched mitochondrial ultrastructure [PMID:29626096], and sensitizes parasites to proguanil [PMID:29626096]. Genetic rescue restores growth only upon reintroduction of a second copy of the gene, whereas decylubiquinone supplementation or a yeast dihydroorotate dehydrogenase bypass fail to rescue, placing L13's essential role in mitoribosomal translation rather than in ubiquinol regeneration or pyrimidine biosynthesis [PMID:29626096]. Beyond this single 2018 study, no further mechanistic detail — including direct demonstration of specific mitochondrially-encoded translation substrates or biochemical mitoribosome assembly data — has been characterized in the available corpus.","teleology":[{"year":2018,"claim":"Establishing where L13 acts was the first requirement; direct localization placed the protein in the mitochondrion, consistent with a mitoribosomal role rather than cytosolic translation.","evidence":"Subcellular localization in P. falciparum using a TetR-DOZI-aptamer conditional system with fluorescence readout","pmids":["29626096"],"confidence":"Medium","gaps":["Does not resolve submitochondrial position or association with the assembled mitoribosome","No biochemical co-purification with other mitoribosomal proteins reported"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2018,"claim":"Whether L13 is functionally essential to the mitochondrion was answered by conditional knockdown, which showed mtETC deficiency and loss of membrane potential and defined the protein as required for mitochondrial functional integrity.","evidence":"Conditional knockdown (TetR-DOZI-aptamer) with mtETC activity assay and mitochondrial membrane potential measurement in P. falciparum","pmids":["29626096"],"confidence":"High","gaps":["mtETC deficiency measured functionally but specific mitochondrially-encoded subunits whose translation fails were not directly quantified","Kinetics linking translation loss to potential collapse not resolved"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2018,"claim":"Whether loss of L13 affects mitochondrial architecture was addressed by ultrastructure, revealing elongated and branched mitochondria and establishing a structural as well as functional dependency.","evidence":"Transmission electron microscopy of conditional knockdown parasites","pmids":["29626096"],"confidence":"High","gaps":["Whether morphological change is a direct consequence of translation loss or a downstream stress response is unresolved"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2018,"claim":"The pharmacological consequence of L13 loss was tested by drug sensitivity, showing proguanil hypersensitivity and linking the essential role to membrane-potential-dependent mitochondrial function.","evidence":"Drug sensitivity assay on conditional knockdown parasites","pmids":["29626096"],"confidence":"Medium","gaps":["Single method for this phenotype; molecular basis of the proguanil interaction not dissected"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2018,"claim":"Whether L13's essential function lies in translation or in a downstream metabolic output was distinguished by rescue: complementation with a second gene copy restored growth, but decylubiquinone and yeast DHODH bypass did not, pinning essentiality on mitoribosomal translation itself.","evidence":"Genetic complementation and metabolic supplementation controls in the conditional knockdown background","pmids":["29626096"],"confidence":"High","gaps":["Direct evidence that L13 participates in a translating mitoribosome (e.g. footprinting, translation assay) is absent","No identification of the specific transcripts whose translation depends on L13"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"The biochemical mechanism by which L13 supports mitoribosomal translation — its integration into the large subunit, the specific mitochondrially-encoded mRNAs it enables, and its assembly partners — remains uncharacterized in the available corpus.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No mitoribosome co-purification or structural placement of L13","No direct translation-level assay of mtETC subunit synthesis upon L13 loss","No interaction partners identified"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["Mitochondrial large ribosomal subunit (mitoribosome)"],"partners":[],"other_free_text":["Essential for parasite viability; knockdown causes growth arrest rescuable only by a second copy of the gene [#4]","Loss confers hypersensitivity to proguanil [#3]","Essential function is independent of ubiquinol regeneration and pyrimidine biosynthesis bypass, as neither decylubiquinone nor yeast DHODH rescues knockdown [#4]"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"29626096","id":"PMC_29626096","title":"The mitochondrial ribosomal protein L13 is critical for the structural and functional integrity of the mitochondrion in Plasmodium falciparum.","date":"2018","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/29626096","citation_count":53,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["L13"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":3474,"output_tokens":1347,"usd":0.015314,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6323,"output_tokens":2378,"usd":0.045532,"stage2_stop_reason":"end_turn"},"total_usd":0.060846,"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\": 2018,\n      \"finding\": \"PF3D7_1004000 (PfmRPL13), a large mitoribosomal protein, localizes to the mitochondrion of P. falciparum, as determined by direct localization experiments.\",\n      \"method\": \"Subcellular localization assay (conditional knockdown system TetR-DOZI-aptamer, fluorescence-based localization)\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct localization experiment in P. falciparum with conditional knockdown, single lab, multiple phenotypic readouts\",\n      \"pmids\": [\"29626096\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"Conditional knockdown of PF3D7_1004000 (PfmRPL13) causes mitochondrial electron transport chain (mtETC) deficiency and loss of mitochondrial membrane potential (Δψm), establishing that L13 is essential for mitochondrial functional integrity in P. falciparum.\",\n      \"method\": \"Conditional knockdown (TetR-DOZI-aptamer system) with mtETC activity assay and mitochondrial membrane potential measurement\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — conditional knockdown with multiple orthogonal functional readouts (mtETC deficiency, Δψm loss, parasite death, rescue with second copy) in a single rigorous study\",\n      \"pmids\": [\"29626096\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"Ablation of PF3D7_1004000 (PfmRPL13) results in an unusually elongated and branched mitochondrial morphology, demonstrating that L13 is required for normal mitochondrial structural integrity.\",\n      \"method\": \"Transmission electron microscopy of conditional knockdown parasites\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — ultrastructural evidence by TEM combined with conditional knockdown, part of a multi-method study with functional validation\",\n      \"pmids\": [\"29626096\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"Knockdown of PF3D7_1004000 (PfmRPL13) renders P. falciparum hypersensitive to proguanil, consistent with L13's role in maintaining mitochondrial membrane potential through mitoribosome-dependent translation of mtETC subunits.\",\n      \"method\": \"Drug sensitivity assay on conditional knockdown parasites (TetR-DOZI-aptamer system)\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — drug sensitivity phenotype linked mechanistically to Δψm loss, single lab, single method for this specific finding\",\n      \"pmids\": [\"29626096\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"Growth arrest of PF3D7_1004000 (PfmRPL13) knockdown parasites was rescued by a second copy of PfmRPL13 but not by supplementation with decylubiquinone or addition of a yeast dihydroorotate dehydrogenase gene, indicating that L13's essential function is specifically tied to mitoribosomal translation rather than ubiquinol regeneration or pyrimidine biosynthesis.\",\n      \"method\": \"Genetic rescue experiment (complementation with second copy; supplementation controls) in conditional knockdown background\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — epistasis-style rescue experiment with positive and negative controls, directly places L13 function in mitoribosomal translation pathway\",\n      \"pmids\": [\"29626096\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"PF3D7_1004000 (L13/PfmRPL13) is an essential large subunit mitoribosomal protein in P. falciparum that localizes to the mitochondrion and is required for mitoribosomal translation of mitochondrially-encoded electron transport chain subunits (cyt b, COXI, COXIII), thereby maintaining mtETC activity, mitochondrial membrane potential, and normal mitochondrial morphology; its loss causes mtETC deficiency, collapse of Δψm, aberrant elongated/branched mitochondrial structure, hypersensitivity to proguanil, and parasite death.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_1004000 (L13) is an essential large mitoribosomal protein of Plasmodium falciparum that localizes to the mitochondrion and is required for mitochondrial functional and structural integrity [#0, #1]. Conditional knockdown of L13 causes electron transport chain deficiency and collapse of the mitochondrial membrane potential [#1], produces an aberrant elongated and branched mitochondrial ultrastructure [#2], and sensitizes parasites to proguanil [#3]. Genetic rescue restores growth only upon reintroduction of a second copy of the gene, whereas decylubiquinone supplementation or a yeast dihydroorotate dehydrogenase bypass fail to rescue, placing L13's essential role in mitoribosomal translation rather than in ubiquinol regeneration or pyrimidine biosynthesis [#4]. Beyond this single 2018 study, no further mechanistic detail — including direct demonstration of specific mitochondrially-encoded translation substrates or biochemical mitoribosome assembly data — has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2018,\n      \"claim\": \"Establishing where L13 acts was the first requirement; direct localization placed the protein in the mitochondrion, consistent with a mitoribosomal role rather than cytosolic translation.\",\n      \"evidence\": \"Subcellular localization in P. falciparum using a TetR-DOZI-aptamer conditional system with fluorescence readout\",\n      \"pmids\": [\"29626096\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Does not resolve submitochondrial position or association with the assembled mitoribosome\",\n        \"No biochemical co-purification with other mitoribosomal proteins reported\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Whether L13 is functionally essential to the mitochondrion was answered by conditional knockdown, which showed mtETC deficiency and loss of membrane potential and defined the protein as required for mitochondrial functional integrity.\",\n      \"evidence\": \"Conditional knockdown (TetR-DOZI-aptamer) with mtETC activity assay and mitochondrial membrane potential measurement in P. falciparum\",\n      \"pmids\": [\"29626096\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"mtETC deficiency measured functionally but specific mitochondrially-encoded subunits whose translation fails were not directly quantified\",\n        \"Kinetics linking translation loss to potential collapse not resolved\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Whether loss of L13 affects mitochondrial architecture was addressed by ultrastructure, revealing elongated and branched mitochondria and establishing a structural as well as functional dependency.\",\n      \"evidence\": \"Transmission electron microscopy of conditional knockdown parasites\",\n      \"pmids\": [\"29626096\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Whether morphological change is a direct consequence of translation loss or a downstream stress response is unresolved\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"The pharmacological consequence of L13 loss was tested by drug sensitivity, showing proguanil hypersensitivity and linking the essential role to membrane-potential-dependent mitochondrial function.\",\n      \"evidence\": \"Drug sensitivity assay on conditional knockdown parasites\",\n      \"pmids\": [\"29626096\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Single method for this phenotype; molecular basis of the proguanil interaction not dissected\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Whether L13's essential function lies in translation or in a downstream metabolic output was distinguished by rescue: complementation with a second gene copy restored growth, but decylubiquinone and yeast DHODH bypass did not, pinning essentiality on mitoribosomal translation itself.\",\n      \"evidence\": \"Genetic complementation and metabolic supplementation controls in the conditional knockdown background\",\n      \"pmids\": [\"29626096\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Direct evidence that L13 participates in a translating mitoribosome (e.g. footprinting, translation assay) is absent\",\n        \"No identification of the specific transcripts whose translation depends on L13\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The biochemical mechanism by which L13 supports mitoribosomal translation — its integration into the large subunit, the specific mitochondrially-encoded mRNAs it enables, and its assembly partners — remains uncharacterized in the available corpus.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No mitoribosome co-purification or structural placement of L13\",\n        \"No direct translation-level assay of mtETC subunit synthesis upon L13 loss\",\n        \"No interaction partners identified\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0003735\", \"supporting_discovery_ids\": [1, 4]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005739\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0032543\", \"supporting_discovery_ids\": [1, 4]},\n      {\"term_id\": \"GO:0022904\", \"supporting_discovery_ids\": [1, 3]},\n      {\"term_id\": \"GO:0007005\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"complexes\": [\n      \"Mitochondrial large ribosomal subunit (mitoribosome)\"\n    ],\n    \"partners\": [],\n    \"other_free_text\": [\n      \"Essential for parasite viability; knockdown causes growth arrest rescuable only by a second copy of the gene [#4]\",\n      \"Loss confers hypersensitivity to proguanil [#3]\",\n      \"Essential function is independent of ubiquinol regeneration and pyrimidine biosynthesis bypass, as neither decylubiquinone nor yeast DHODH rescues knockdown [#4]\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1004000","name":null,"product":"60S ribosomal protein L13, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1202400","name":null,"product":"60S ribosomal protein L13, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0802800","name":null,"product":"60S ribosomal protein L13, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"","evaluation":null}