{"gene":"PF3D7_1239100","run_date":"2026-09-08T16:26:55","timeline":{"discoveries":[{"year":2022,"finding":"MRPL23 (PF3D7_1239100) localizes to the mitochondrion of P. falciparum, as determined by direct localization experiments.","method":"Subcellular localization (direct experimental localization to mitochondrion)","journal":"PloS one","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — direct localization experiment in a single study, single lab, method details not fully specified in abstract","pmids":["36201550"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2022,"finding":"Conditional knockdown of MRPL23 (PF3D7_1239100) leads to reduced cytochrome bc1 complex activity and increased parasite sensitivity to bc1 inhibitors atovaquone and ELQ-300, establishing a functional role for MRPL23 in mitochondrial electron transport chain activity.","method":"Conditional knockdown with enzymatic activity assay (cytochrome bc1 complex activity) and drug sensitivity assay","journal":"PloS one","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — conditional knockdown with two orthogonal functional readouts (enzymatic activity and drug sensitivity), single lab","pmids":["36201550"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2022,"finding":"Knockdown of MRPL23 (PF3D7_1239100) in the early phase upregulates many mitochondrial rRNAs and several mitoribosomal proteins, in contrast to RSM22 knockdown which downregulates them — suggesting MRPL23 plays a non-redundant role in P. falciparum mitoribosome assembly distinct from that of the assembly factor RSM22.","method":"Conditional knockdown followed by RNA sequencing (transcriptomic analysis of nuclear and mitochondrial genomes)","journal":"PloS one","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — RNA-seq after conditional knockdown, contrasted with a second protein knockdown as an internal comparator, single lab","pmids":["36201550"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2022,"finding":"Late-stage knockdown of MRPL23 (PF3D7_1239100) causes broad transcriptional defects in essential metabolic pathways and mitochondrial functions, ultimately leading to parasite death.","method":"Conditional knockdown with RNA sequencing and parasite viability assay","journal":"PloS one","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — conditional knockdown with transcriptomic readout and parasite death phenotype, single lab, two orthogonal readouts","pmids":["36201550"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"MRPL23 (PF3D7_1239100) is a mitochondrion-localized large subunit mitoribosomal protein in P. falciparum that is required for proper cytochrome bc1 complex activity, plays a non-redundant role in mitoribosome assembly (distinct from the assembly factor RSM22), and is essential for parasite survival, as its loss leads to broad mitochondrial and metabolic dysfunction."},"narrative":{"mechanistic_narrative":"MRPL23 (PF3D7_1239100) is a mitochondrion-localized large-subunit mitoribosomal protein of Plasmodium falciparum that supports mitochondrial gene expression and electron transport chain function [PMID:36201550]. Conditional knockdown reduces cytochrome bc1 complex activity and sensitizes parasites to the bc1 inhibitors atovaquone and ELQ-300, linking MRPL23 function to maintenance of mitochondrial respiratory activity [PMID:36201550]. MRPL23 plays a non-redundant role in mitoribosome assembly distinct from the assembly factor RSM22: early knockdown of MRPL23 upregulates mitochondrial rRNAs and several mitoribosomal proteins, whereas RSM22 knockdown downregulates them [PMID:36201550]. Late-stage loss of MRPL23 produces broad transcriptional defects across essential metabolic and mitochondrial pathways and culminates in parasite death, indicating an essential cellular role [PMID:36201550]. Beyond these findings, no structural model, direct RNA- or protein-binding data, or defined position within the mitoribosome has been characterized for PF3D7_1239100 in the available corpus.","teleology":[{"year":2022,"claim":"Establishing where MRPL23 acts was the first step in assigning it a mitochondrial function rather than inferring one from its annotation.","evidence":"Direct subcellular localization in P. falciparum","pmids":["36201550"],"confidence":"Medium","gaps":["Localization method details not fully specified and from a single study/lab","Sub-mitochondrial position (matrix vs. membrane-associated mitoribosome) not resolved","No demonstration of physical incorporation into an assembled mitoribosome"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2022,"claim":"Linking MRPL23 to a measurable respiratory output showed its mitochondrial role has functional consequences for electron transport.","evidence":"Conditional knockdown with cytochrome bc1 activity assay and atovaquone/ELQ-300 drug sensitivity","pmids":["36201550"],"confidence":"Medium","gaps":["Whether reduced bc1 activity is direct or a downstream consequence of impaired mitochondrial translation is not distinguished","No identification of the specific mitochondrially encoded bc1 subunits affected","Single lab, single study"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2022,"claim":"Contrasting MRPL23 knockdown against RSM22 knockdown separated its role in mitoribosome biogenesis from that of a dedicated assembly factor.","evidence":"Conditional knockdown followed by RNA-seq of nuclear and mitochondrial genomes, with RSM22 knockdown as internal comparator","pmids":["36201550"],"confidence":"Medium","gaps":["The opposing transcriptomic responses are correlative; the mechanistic basis of the non-redundancy is not defined","No direct assay of mitoribosome assembly state or rRNA processing","Whether transcript changes reflect assembly defects versus compensatory regulation is unresolved"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2022,"claim":"Demonstrating that late knockdown kills the parasite established MRPL23 as essential and placed its loss upstream of broad metabolic collapse.","evidence":"Conditional knockdown with RNA-seq and parasite viability assay","pmids":["36201550"],"confidence":"Medium","gaps":["The broad transcriptional defects are downstream signatures, not a defined causal pathway to death","Essentiality shown by knockdown in one strain/stage; not tested across life-cycle stages","Single lab, single study"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"The physical role of MRPL23 within the P. falciparum mitoribosome and its direct binding partners or RNA contacts remain undefined.","evidence":"No direct structural, interaction, or reconstitution data in the corpus","pmids":[],"confidence":"Low","gaps":["No structural model or cryo-EM placement within the large subunit","No direct rRNA- or protein-binding evidence","No reciprocal validation of mitoribosome membership beyond localization and knockdown phenotypes"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["mitochondrial large ribosomal subunit (mitoribosome)"],"partners":[],"other_free_text":["Non-redundant role in mitoribosome assembly distinct from the assembly factor RSM22 [#2]","Required for cytochrome bc1 complex activity; knockdown increases sensitivity to atovaquone and ELQ-300 [#1]","Essential for parasite survival; late knockdown causes broad metabolic/mitochondrial transcriptional defects and death [#3]"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"36201550","id":"PMC_36201550","title":"Transcriptional changes in Plasmodium falciparum upon conditional knock down of mitochondrial ribosomal proteins RSM22 and L23.","date":"2022","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/36201550","citation_count":15,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["L23","PfMRPL23"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"37108644","id":"","title":"Ribosome Specialization in Protozoa Parasites.","date":"2023","source":"International journal of molecular sciences","url":"https://pubmed.ncbi.nlm.nih.gov/37108644","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["MRPL23"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":4200,"output_tokens":1001,"usd":0.013808,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5819,"output_tokens":2138,"usd":0.041272,"stage2_stop_reason":"end_turn"},"total_usd":0.05508,"stage1_batch_id":"msgbatch_01NE1MTa8x1hW7Lo4tAaNzY1","stage2_batch_id":"msgbatch_0141vaQdeFvbo2q39AinvXM9","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2022,\n      \"finding\": \"MRPL23 (PF3D7_1239100) localizes to the mitochondrion of P. falciparum, as determined by direct localization experiments.\",\n      \"method\": \"Subcellular localization (direct experimental localization to mitochondrion)\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — direct localization experiment in a single study, single lab, method details not fully specified in abstract\",\n      \"pmids\": [\"36201550\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"Conditional knockdown of MRPL23 (PF3D7_1239100) leads to reduced cytochrome bc1 complex activity and increased parasite sensitivity to bc1 inhibitors atovaquone and ELQ-300, establishing a functional role for MRPL23 in mitochondrial electron transport chain activity.\",\n      \"method\": \"Conditional knockdown with enzymatic activity assay (cytochrome bc1 complex activity) and drug sensitivity assay\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — conditional knockdown with two orthogonal functional readouts (enzymatic activity and drug sensitivity), single lab\",\n      \"pmids\": [\"36201550\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"Knockdown of MRPL23 (PF3D7_1239100) in the early phase upregulates many mitochondrial rRNAs and several mitoribosomal proteins, in contrast to RSM22 knockdown which downregulates them — suggesting MRPL23 plays a non-redundant role in P. falciparum mitoribosome assembly distinct from that of the assembly factor RSM22.\",\n      \"method\": \"Conditional knockdown followed by RNA sequencing (transcriptomic analysis of nuclear and mitochondrial genomes)\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — RNA-seq after conditional knockdown, contrasted with a second protein knockdown as an internal comparator, single lab\",\n      \"pmids\": [\"36201550\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"Late-stage knockdown of MRPL23 (PF3D7_1239100) causes broad transcriptional defects in essential metabolic pathways and mitochondrial functions, ultimately leading to parasite death.\",\n      \"method\": \"Conditional knockdown with RNA sequencing and parasite viability assay\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — conditional knockdown with transcriptomic readout and parasite death phenotype, single lab, two orthogonal readouts\",\n      \"pmids\": [\"36201550\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"MRPL23 (PF3D7_1239100) is a mitochondrion-localized large subunit mitoribosomal protein in P. falciparum that is required for proper cytochrome bc1 complex activity, plays a non-redundant role in mitoribosome assembly (distinct from the assembly factor RSM22), and is essential for parasite survival, as its loss leads to broad mitochondrial and metabolic dysfunction.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"MRPL23 (PF3D7_1239100) is a mitochondrion-localized large-subunit mitoribosomal protein of Plasmodium falciparum that supports mitochondrial gene expression and electron transport chain function [#0, #1]. Conditional knockdown reduces cytochrome bc1 complex activity and sensitizes parasites to the bc1 inhibitors atovaquone and ELQ-300, linking MRPL23 function to maintenance of mitochondrial respiratory activity [#1]. MRPL23 plays a non-redundant role in mitoribosome assembly distinct from the assembly factor RSM22: early knockdown of MRPL23 upregulates mitochondrial rRNAs and several mitoribosomal proteins, whereas RSM22 knockdown downregulates them [#2]. Late-stage loss of MRPL23 produces broad transcriptional defects across essential metabolic and mitochondrial pathways and culminates in parasite death, indicating an essential cellular role [#3]. Beyond these findings, no structural model, direct RNA- or protein-binding data, or defined position within the mitoribosome has been characterized for PF3D7_1239100 in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2022,\n      \"claim\": \"Establishing where MRPL23 acts was the first step in assigning it a mitochondrial function rather than inferring one from its annotation.\",\n      \"evidence\": \"Direct subcellular localization in P. falciparum\",\n      \"pmids\": [\"36201550\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Localization method details not fully specified and from a single study/lab\",\n        \"Sub-mitochondrial position (matrix vs. membrane-associated mitoribosome) not resolved\",\n        \"No demonstration of physical incorporation into an assembled mitoribosome\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Linking MRPL23 to a measurable respiratory output showed its mitochondrial role has functional consequences for electron transport.\",\n      \"evidence\": \"Conditional knockdown with cytochrome bc1 activity assay and atovaquone/ELQ-300 drug sensitivity\",\n      \"pmids\": [\"36201550\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Whether reduced bc1 activity is direct or a downstream consequence of impaired mitochondrial translation is not distinguished\",\n        \"No identification of the specific mitochondrially encoded bc1 subunits affected\",\n        \"Single lab, single study\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Contrasting MRPL23 knockdown against RSM22 knockdown separated its role in mitoribosome biogenesis from that of a dedicated assembly factor.\",\n      \"evidence\": \"Conditional knockdown followed by RNA-seq of nuclear and mitochondrial genomes, with RSM22 knockdown as internal comparator\",\n      \"pmids\": [\"36201550\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"The opposing transcriptomic responses are correlative; the mechanistic basis of the non-redundancy is not defined\",\n        \"No direct assay of mitoribosome assembly state or rRNA processing\",\n        \"Whether transcript changes reflect assembly defects versus compensatory regulation is unresolved\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Demonstrating that late knockdown kills the parasite established MRPL23 as essential and placed its loss upstream of broad metabolic collapse.\",\n      \"evidence\": \"Conditional knockdown with RNA-seq and parasite viability assay\",\n      \"pmids\": [\"36201550\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"The broad transcriptional defects are downstream signatures, not a defined causal pathway to death\",\n        \"Essentiality shown by knockdown in one strain/stage; not tested across life-cycle stages\",\n        \"Single lab, single study\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The physical role of MRPL23 within the P. falciparum mitoribosome and its direct binding partners or RNA contacts remain undefined.\",\n      \"evidence\": \"No direct structural, interaction, or reconstitution data in the corpus\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No structural model or cryo-EM placement within the large subunit\",\n        \"No direct rRNA- or protein-binding evidence\",\n        \"No reciprocal validation of mitoribosome membership beyond localization and knockdown phenotypes\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0003735\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005739\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0032543\", \"supporting_discovery_ids\": [2, 3]},\n      {\"term_id\": \"GO:0022904\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"complexes\": [\n      \"mitochondrial large ribosomal subunit (mitoribosome)\"\n    ],\n    \"partners\": [],\n    \"other_free_text\": [\n      \"Non-redundant role in mitoribosome assembly distinct from the assembly factor RSM22 [#2]\",\n      \"Required for cytochrome bc1 complex activity; knockdown increases sensitivity to atovaquone and ELQ-300 [#1]\",\n      \"Essential for parasite survival; late knockdown causes broad metabolic/mitochondrial transcriptional defects and death [#3]\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1239100","name":null,"product":"ribosomal protein L23, mitochondrial","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1453600","name":null,"product":"ribosomal protein L23, mitochondrial, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1458900","name":null,"product":"ribosomal protein L23, mitochondrial, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"MRPL23","evaluation":null}