{"gene":"PF3D7_0306000","run_date":"2026-09-08T16:26:55","timeline":{"discoveries":[{"year":2021,"finding":"Complexome profiling of Plasmodium falciparum mitochondria identified QCR8 (PF3D7_0306000) as a subunit of the cytochrome bc1 Complex III (respiratory chain complex III), with divergent composition relative to traditional model organisms and up to 40-fold higher prevalence of respiratory chain complex components in gametocytes compared to asexual blood stages.","method":"Complexome profiling (native protein complex mapping by mass spectrometry across asexual blood stages and gametocyte stages)","journal":"Nature communications","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — complexome profiling is a systematic, quantitative co-fractionation/MS approach establishing complex membership; single study but applied systematically across multiple life stages with quantitative readout","pmids":["34155201"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2025,"finding":"Solvent proteome profiling (SPP) showed that QCR8 (PF3D7_0306000) is significantly stabilised upon atovaquone treatment of P. falciparum lysates (p.adj = 6.03e-04, log2FC = 0.55), confirming its physical membership within the cytochrome bc1 Complex III that is targeted by atovaquone.","method":"Solvent-induced proteome profiling (SPP) — ligand-induced protein thermal/solvent stability shift detected by mass spectrometry in parasite lysates treated with atovaquone","journal":"International journal for parasitology. Drugs and drug resistance","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — quantitative proteomics stability-shift assay with statistical significance; single study, single method, but corroborates complex membership established by independent complexome profiling","pmids":["41308470"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"QCR8 (PF3D7_0306000) is a subunit of the cytochrome bc1 Complex III in the Plasmodium falciparum mitochondrion, as established by complexome profiling and confirmed by atovaquone-induced protein stabilisation in solvent proteome profiling; its complex is up-regulated in gametocytes relative to asexual blood stages, but no further mechanistic detail about its specific molecular function within the complex has been experimentally determined."},"narrative":{"mechanistic_narrative":"QCR8 (PF3D7_0306000) is a subunit of the cytochrome bc1 respiratory chain Complex III in the Plasmodium falciparum mitochondrion, assigned by complexome profiling of native mitochondrial complexes, which also revealed a composition divergent from traditional model organisms and up to 40-fold higher abundance of respiratory chain components in gametocytes relative to asexual blood stages [PMID:34155201]. Its physical membership in this complex is independently supported by solvent proteome profiling, in which QCR8 is significantly stabilized upon treatment of parasite lysates with the Complex III inhibitor atovaquone [PMID:41308470]. Beyond its assignment as a Complex III subunit and this stage-dependent enrichment, no specific molecular function of QCR8 within the complex has been characterized in the available corpus.","teleology":[{"year":2021,"claim":"Whether PF3D7_0306000 belongs to a defined mitochondrial complex was unknown; systematic native-complex mapping established it as a subunit of the cytochrome bc1 Complex III and revealed marked up-regulation of the respiratory chain in gametocytes.","evidence":"Complexome profiling by co-fractionation and mass spectrometry across asexual blood stages and gametocytes","pmids":["34155201"],"confidence":"Medium","gaps":["Does not define the specific structural or catalytic role of QCR8 within Complex III","Does not establish whether QCR8 is essential for complex assembly or activity","Functional consequence of gametocyte-stage enrichment not tested"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2025,"claim":"Whether the complexome assignment reflected genuine, drug-relevant physical association was unresolved; ligand-induced stability profiling confirmed QCR8 is stabilized by the Complex III inhibitor atovaquone, corroborating its membership in the atovaquone-targeted complex.","evidence":"Solvent proteome profiling (SPP) of atovaquone-treated P. falciparum lysates detected by mass spectrometry","pmids":["41308470"],"confidence":"Medium","gaps":["Does not show QCR8 directly binds atovaquone versus stabilization via the complex","Does not establish QCR8's contribution to atovaquone sensitivity or resistance","No reconstitution or subunit-level functional assay"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"The specific molecular function of QCR8 within Complex III, its requirement for complex assembly or electron transfer, and the significance of its gametocyte enrichment remain uncharacterized in the available corpus.","evidence":"No direct functional, structural, or genetic study of QCR8 present in the timeline","pmids":[],"confidence":"Medium","gaps":["No genetic knockout or knockdown of QCR8 reported","No structural model of QCR8 within the P. falciparum Complex III","No defined molecular activity beyond complex membership"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["Cytochrome bc1 respiratory chain Complex III"],"partners":[],"other_free_text":["Assigned as a Complex III subunit by complexome profiling of P. falciparum mitochondria [#0]","Respiratory chain Complex III components up to 40-fold more abundant in gametocytes than asexual blood stages [#0]","Stabilized upon atovaquone treatment in solvent proteome profiling, consistent with membership in the atovaquone-targeted Complex III [#1]","No subunit-specific molecular function of QCR8 within Complex III established in the available corpus"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"34155201","id":"PMC_34155201","title":"Composition and stage dynamics of mitochondrial complexes in Plasmodium falciparum.","date":"2021","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/34155201","citation_count":92,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"41308470","id":"","title":"Validation of solvent proteome profiling for antimalarial drug target deconvolution.","date":"2025","source":"International journal for parasitology. Drugs and drug resistance","url":"https://pubmed.ncbi.nlm.nih.gov/41308470","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["QCR8"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":4644,"output_tokens":702,"usd":0.012231,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5343,"output_tokens":1545,"usd":0.03267,"stage2_stop_reason":"end_turn"},"total_usd":0.044901,"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\": 2021,\n      \"finding\": \"Complexome profiling of Plasmodium falciparum mitochondria identified QCR8 (PF3D7_0306000) as a subunit of the cytochrome bc1 Complex III (respiratory chain complex III), with divergent composition relative to traditional model organisms and up to 40-fold higher prevalence of respiratory chain complex components in gametocytes compared to asexual blood stages.\",\n      \"method\": \"Complexome profiling (native protein complex mapping by mass spectrometry across asexual blood stages and gametocyte stages)\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — complexome profiling is a systematic, quantitative co-fractionation/MS approach establishing complex membership; single study but applied systematically across multiple life stages with quantitative readout\",\n      \"pmids\": [\"34155201\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"Solvent proteome profiling (SPP) showed that QCR8 (PF3D7_0306000) is significantly stabilised upon atovaquone treatment of P. falciparum lysates (p.adj = 6.03e-04, log2FC = 0.55), confirming its physical membership within the cytochrome bc1 Complex III that is targeted by atovaquone.\",\n      \"method\": \"Solvent-induced proteome profiling (SPP) — ligand-induced protein thermal/solvent stability shift detected by mass spectrometry in parasite lysates treated with atovaquone\",\n      \"journal\": \"International journal for parasitology. Drugs and drug resistance\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — quantitative proteomics stability-shift assay with statistical significance; single study, single method, but corroborates complex membership established by independent complexome profiling\",\n      \"pmids\": [\"41308470\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"QCR8 (PF3D7_0306000) is a subunit of the cytochrome bc1 Complex III in the Plasmodium falciparum mitochondrion, as established by complexome profiling and confirmed by atovaquone-induced protein stabilisation in solvent proteome profiling; its complex is up-regulated in gametocytes relative to asexual blood stages, but no further mechanistic detail about its specific molecular function within the complex has been experimentally determined.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"QCR8 (PF3D7_0306000) is a subunit of the cytochrome bc1 respiratory chain Complex III in the Plasmodium falciparum mitochondrion, assigned by complexome profiling of native mitochondrial complexes, which also revealed a composition divergent from traditional model organisms and up to 40-fold higher abundance of respiratory chain components in gametocytes relative to asexual blood stages [#0]. Its physical membership in this complex is independently supported by solvent proteome profiling, in which QCR8 is significantly stabilized upon treatment of parasite lysates with the Complex III inhibitor atovaquone [#1]. Beyond its assignment as a Complex III subunit and this stage-dependent enrichment, no specific molecular function of QCR8 within the complex has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2021,\n      \"claim\": \"Whether PF3D7_0306000 belongs to a defined mitochondrial complex was unknown; systematic native-complex mapping established it as a subunit of the cytochrome bc1 Complex III and revealed marked up-regulation of the respiratory chain in gametocytes.\",\n      \"evidence\": \"Complexome profiling by co-fractionation and mass spectrometry across asexual blood stages and gametocytes\",\n      \"pmids\": [\"34155201\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Does not define the specific structural or catalytic role of QCR8 within Complex III\",\n        \"Does not establish whether QCR8 is essential for complex assembly or activity\",\n        \"Functional consequence of gametocyte-stage enrichment not tested\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Whether the complexome assignment reflected genuine, drug-relevant physical association was unresolved; ligand-induced stability profiling confirmed QCR8 is stabilized by the Complex III inhibitor atovaquone, corroborating its membership in the atovaquone-targeted complex.\",\n      \"evidence\": \"Solvent proteome profiling (SPP) of atovaquone-treated P. falciparum lysates detected by mass spectrometry\",\n      \"pmids\": [\"41308470\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Does not show QCR8 directly binds atovaquone versus stabilization via the complex\",\n        \"Does not establish QCR8's contribution to atovaquone sensitivity or resistance\",\n        \"No reconstitution or subunit-level functional assay\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The specific molecular function of QCR8 within Complex III, its requirement for complex assembly or electron transfer, and the significance of its gametocyte enrichment remain uncharacterized in the available corpus.\",\n      \"evidence\": \"No direct functional, structural, or genetic study of QCR8 present in the timeline\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No genetic knockout or knockdown of QCR8 reported\",\n        \"No structural model of QCR8 within the P. falciparum Complex III\",\n        \"No defined molecular activity beyond complex membership\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [\n      {\"term_id\": \"GO:0005739\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0022904\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"complexes\": [\"Cytochrome bc1 respiratory chain Complex III\"],\n    \"partners\": [],\n    \"other_free_text\": [\n      \"Assigned as a Complex III subunit by complexome profiling of P. falciparum mitochondria [#0]\",\n      \"Respiratory chain Complex III components up to 40-fold more abundant in gametocytes than asexual blood stages [#0]\",\n      \"Stabilized upon atovaquone treatment in solvent proteome profiling, consistent with membership in the atovaquone-targeted Complex III [#1]\",\n      \"No subunit-specific molecular function of QCR8 within Complex III established in the available corpus\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0306000","name":null,"product":"cytochrome b-c1 complex subunit 8, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0404400","name":null,"product":"cytochrome b-c1 complex subunit 8, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"QCR8","evaluation":null}