{"gene":"TG_215280","gene_symbol":"SDHB","run_date":"2026-09-08T11:06:29","timeline":{"discoveries":[{"year":2023,"finding":"SDHB (TgSdhB) is a validated subunit of the Toxoplasma gondii succinate dehydrogenase (SDH/complex II), and its integrity is required for SDH assembly and activity; disruption impairs mitochondrial respiration and triggers spontaneous bradyzoite differentiation.","method":"Genetic disruption (conditional knockdown/knockout), SDH activity assays, mitochondrial respiration measurements, differentiation assays","journal":"PLoS pathogens","confidence":"High","confidence_rationale":"Tier 2 / Moderate — multiple orthogonal functional assays (assembly, enzymatic activity, respiration, differentiation phenotype) in a single study with clean loss-of-function approach","pmids":["38079448"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2024,"finding":"TgSdhB (catalytic core subunit) requires the myzozoan-specific membrane protein TgMPODD to be anchored to the inner mitochondrial membrane; depletion of TgMPODD abolishes SDH activity and detaches TgSdhA/TgSdhB from the membrane anchor of the complex.","method":"Co-immunoprecipitation, proximity ligation/BioID-type assays, conditional knockdown of TgMPODD, SDH activity assays, membrane fractionation, O2 consumption measurements","journal":"Open biology","confidence":"High","confidence_rationale":"Tier 2 / Moderate — reciprocal interaction mapping, loss-of-function with enzymatic activity and fractionation readouts in a single rigorous study","pmids":["38835243"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2021,"finding":"Complexome profiling of Toxoplasma mitochondria placed SDHB within complex II, identifying its co-migration with other SDH subunits and confirming its assignment to the electron transport chain complex II.","method":"Complexome profiling (native gel electrophoresis coupled with mass spectrometry)","journal":"PLoS pathogens","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — complexome profiling is a single proteomic method identifying co-migration, providing compositional but limited mechanistic resolution","pmids":["33651838"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"current_model":"TgSdhB is the canonical iron-sulfur subunit of the Toxoplasma gondii succinate dehydrogenase (complex II), forming part of the catalytic core together with TgSdhA; unlike in canonical eukaryotes, the complex lacks SdhC/SdhD homologs and instead uses lineage-specific membrane-anchoring subunits (including the myzozoan-specific TgMPODD) to attach TgSdhA/TgSdhB to the inner mitochondrial membrane, with the intact complex being required for SDH enzymatic activity, mitochondrial respiration, and suppression of spontaneous bradyzoite differentiation."},"narrative":{"mechanistic_narrative":"TgSdhB is a validated iron-sulfur subunit of the Toxoplasma gondii succinate dehydrogenase (complex II), first assigned to complex II by complexome profiling showing co-migration with other SDH subunits [PMID:33651838] and confirmed as an integral catalytic-core component whose integrity is required for SDH assembly and enzymatic activity [PMID:38079448]. Disruption of TgSdhB impairs mitochondrial respiration and triggers spontaneous bradyzoite differentiation, linking complex II function to suppression of stage conversion [PMID:38079448]. Unlike canonical eukaryotic SDH, membrane attachment of the TgSdhA/TgSdhB catalytic core depends on the myzozoan-specific membrane protein TgMPODD; depletion of TgMPODD detaches TgSdhA/TgSdhB from the membrane anchor and abolishes SDH activity [PMID:38835243].","teleology":[{"year":2021,"claim":"Establishing which mitochondrial complex TgSdhB belongs to was the first step, resolving its compositional assignment within the Toxoplasma electron transport chain.","evidence":"complexome profiling (native gel electrophoresis coupled with mass spectrometry) of Toxoplasma mitochondria","pmids":["33651838"],"confidence":"Medium","gaps":["co-migration is compositional, not functional, evidence","does not establish catalytic contribution or membrane-anchoring architecture"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2023,"claim":"Moving from compositional assignment to function, loss-of-function experiments established that TgSdhB integrity is required for SDH assembly, enzymatic activity, respiration, and suppression of bradyzoite differentiation.","evidence":"conditional genetic disruption with SDH activity assays, respiration measurements, and differentiation assays in T. gondii","pmids":["38079448"],"confidence":"High","gaps":["does not resolve how the catalytic core attaches to the inner mitochondrial membrane","molecular basis of the differentiation phenotype not defined"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2024,"claim":"Addressing the atypical architecture of the parasite complex, TgMPODD was identified as the lineage-specific membrane anchor tethering the TgSdhA/TgSdhB core to the inner mitochondrial membrane, explaining SDH membrane attachment in the absence of canonical SdhC/SdhD.","evidence":"co-immunoprecipitation, BioID-type proximity assays, conditional knockdown of TgMPODD, membrane fractionation, SDH activity and O2 consumption measurements","pmids":["38835243"],"confidence":"High","gaps":["structural model of the anchored complex not determined","stoichiometry of the myzozoan-specific subunits not resolved"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":null,"claim":"The molecular mechanism linking loss of SDH/complex II activity to spontaneous bradyzoite differentiation remains unresolved.","evidence":"","pmids":[],"confidence":"High","gaps":["no signaling pathway connecting respiratory defect to stage conversion identified","no structural characterization of TgSdhB or the assembled parasite complex II"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["Succinate dehydrogenase (complex II)"],"partners":["TGSDHA (CATALYTIC CORE PARTNER SUBUNIT)","TGMPODD (MYZOZOAN-SPECIFIC INNER MEMBRANE ANCHOR)"],"other_free_text":["Toxoplasma complex II lacks canonical SdhC/SdhD homologs and uses lineage-specific membrane-anchoring subunits [#1].","Disruption of TgSdhB triggers spontaneous bradyzoite differentiation, linking complex II activity to stage conversion [#0]."]},"strain_conflicts":[]},"prefetch_data":{},"corpus_meta":[{"pmid":"33651838","id":"PMC_33651838","title":"Complexome profile of Toxoplasma gondii mitochondria identifies divergent subunits of respiratory chain complexes including new subunits of cytochrome bc1 complex.","date":"2021","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/33651838","citation_count":53,"is_preprint":false},{"pmid":"38079448","id":"PMC_38079448","title":"Functional and biochemical characterization of the Toxoplasma gondii succinate dehydrogenase complex.","date":"2023","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/38079448","citation_count":11,"is_preprint":false},{"pmid":"38835243","id":"PMC_38835243","title":"A myzozoan-specific protein is an essential membrane-anchoring component of the succinate dehydrogenase complex in Toxoplasma parasites.","date":"2024","source":"Open biology","url":"https://pubmed.ncbi.nlm.nih.gov/38835243","citation_count":4,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":3873,"output_tokens":890,"usd":0.012485,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5746,"output_tokens":2003,"usd":0.039403,"stage2_stop_reason":"end_turn"},"total_usd":0.051888,"stage1_batch_id":"msgbatch_01WokvBYTB6JLnYrpD4rXnyV","stage2_batch_id":"msgbatch_01M7hsQDvz6AqVC9DLVjQzzc","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2023,\n      \"finding\": \"SDHB (TgSdhB) is a validated subunit of the Toxoplasma gondii succinate dehydrogenase (SDH/complex II), and its integrity is required for SDH assembly and activity; disruption impairs mitochondrial respiration and triggers spontaneous bradyzoite differentiation.\",\n      \"method\": \"Genetic disruption (conditional knockdown/knockout), SDH activity assays, mitochondrial respiration measurements, differentiation assays\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple orthogonal functional assays (assembly, enzymatic activity, respiration, differentiation phenotype) in a single study with clean loss-of-function approach\",\n      \"pmids\": [\"38079448\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"TgSdhB (catalytic core subunit) requires the myzozoan-specific membrane protein TgMPODD to be anchored to the inner mitochondrial membrane; depletion of TgMPODD abolishes SDH activity and detaches TgSdhA/TgSdhB from the membrane anchor of the complex.\",\n      \"method\": \"Co-immunoprecipitation, proximity ligation/BioID-type assays, conditional knockdown of TgMPODD, SDH activity assays, membrane fractionation, O2 consumption measurements\",\n      \"journal\": \"Open biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal interaction mapping, loss-of-function with enzymatic activity and fractionation readouts in a single rigorous study\",\n      \"pmids\": [\"38835243\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"Complexome profiling of Toxoplasma mitochondria placed SDHB within complex II, identifying its co-migration with other SDH subunits and confirming its assignment to the electron transport chain complex II.\",\n      \"method\": \"Complexome profiling (native gel electrophoresis coupled with mass spectrometry)\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — complexome profiling is a single proteomic method identifying co-migration, providing compositional but limited mechanistic resolution\",\n      \"pmids\": [\"33651838\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"TgSdhB is the canonical iron-sulfur subunit of the Toxoplasma gondii succinate dehydrogenase (complex II), forming part of the catalytic core together with TgSdhA; unlike in canonical eukaryotes, the complex lacks SdhC/SdhD homologs and instead uses lineage-specific membrane-anchoring subunits (including the myzozoan-specific TgMPODD) to attach TgSdhA/TgSdhB to the inner mitochondrial membrane, with the intact complex being required for SDH enzymatic activity, mitochondrial respiration, and suppression of spontaneous bradyzoite differentiation.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"TgSdhB is a validated iron-sulfur subunit of the Toxoplasma gondii succinate dehydrogenase (complex II), first assigned to complex II by complexome profiling showing co-migration with other SDH subunits [#2] and confirmed as an integral catalytic-core component whose integrity is required for SDH assembly and enzymatic activity [#0]. Disruption of TgSdhB impairs mitochondrial respiration and triggers spontaneous bradyzoite differentiation, linking complex II function to suppression of stage conversion [#0]. Unlike canonical eukaryotic SDH, membrane attachment of the TgSdhA/TgSdhB catalytic core depends on the myzozoan-specific membrane protein TgMPODD; depletion of TgMPODD detaches TgSdhA/TgSdhB from the membrane anchor and abolishes SDH activity [#1].\",\n  \"teleology\": [\n    {\n      \"year\": 2021,\n      \"claim\": \"Establishing which mitochondrial complex TgSdhB belongs to was the first step, resolving its compositional assignment within the Toxoplasma electron transport chain.\",\n      \"evidence\": \"complexome profiling (native gel electrophoresis coupled with mass spectrometry) of Toxoplasma mitochondria\",\n      \"pmids\": [\"33651838\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"co-migration is compositional, not functional, evidence\",\n        \"does not establish catalytic contribution or membrane-anchoring architecture\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Moving from compositional assignment to function, loss-of-function experiments established that TgSdhB integrity is required for SDH assembly, enzymatic activity, respiration, and suppression of bradyzoite differentiation.\",\n      \"evidence\": \"conditional genetic disruption with SDH activity assays, respiration measurements, and differentiation assays in T. gondii\",\n      \"pmids\": [\"38079448\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"does not resolve how the catalytic core attaches to the inner mitochondrial membrane\",\n        \"molecular basis of the differentiation phenotype not defined\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Addressing the atypical architecture of the parasite complex, TgMPODD was identified as the lineage-specific membrane anchor tethering the TgSdhA/TgSdhB core to the inner mitochondrial membrane, explaining SDH membrane attachment in the absence of canonical SdhC/SdhD.\",\n      \"evidence\": \"co-immunoprecipitation, BioID-type proximity assays, conditional knockdown of TgMPODD, membrane fractionation, SDH activity and O2 consumption measurements\",\n      \"pmids\": [\"38835243\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"structural model of the anchored complex not determined\",\n        \"stoichiometry of the myzozoan-specific subunits not resolved\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The molecular mechanism linking loss of SDH/complex II activity to spontaneous bradyzoite differentiation remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"no signaling pathway connecting respiratory defect to stage conversion identified\",\n        \"no structural characterization of TgSdhB or the assembled parasite complex II\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0008177\", \"supporting_discovery_ids\": [0, 2], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]},\n      {\"term_id\": \"GO:0009055\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005743\", \"supporting_discovery_ids\": [1], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]},\n      {\"term_id\": \"GO:0045273\", \"supporting_discovery_ids\": [0, 2], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0006121\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]},\n      {\"term_id\": \"GO:0022904\", \"supporting_discovery_ids\": [0, 2], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"complexes\": [\n      \"Succinate dehydrogenase (complex II)\"\n    ],\n    \"partners\": [\n      \"TgSdhA (catalytic core partner subunit)\",\n      \"TgMPODD (myzozoan-specific inner membrane anchor)\"\n    ],\n    \"other_free_text\": [\n      \"Toxoplasma complex II lacks canonical SdhC/SdhD homologs and uses lineage-specific membrane-anchoring subunits [#1].\",\n      \"Disruption of TgSdhB triggers spontaneous bradyzoite differentiation, linking complex II activity to stage conversion [#0].\"\n    ]\n  },\n  \"strain_conflicts\": []\n}","audit_flag":null,"strains":[{"strain":"ME49","gene_id":"TGME49_215280","name":"SDHB","product":"succinate dehydrogenase [ubiquinone] iron-sulfur subunit SDHB","uniprot_acc":"A0A125YH79","chromosome":"TGME49_chrX","start_pos":6870782},{"strain":"GT1","gene_id":"TGGT1_215280","name":null,"product":"succinate dehydrogenase [ubiquinone] iron-sulfur protein","uniprot_acc":null,"chromosome":"TGGT1_chrX","start_pos":6762757},{"strain":"RH88","gene_id":"TGRH88_039360","name":null,"product":"succinate dehydrogenase [ubiquinone] iron-sulfur protein","uniprot_acc":null,"chromosome":"CM023091","start_pos":662267},{"strain":"VEG","gene_id":"TGVEG_215280","name":null,"product":"succinate dehydrogenase [ubiquinone] iron-sulfur protein","uniprot_acc":"B9PZR3","chromosome":"TGVEG_chrX","start_pos":6802582}]}