{"gene":"TG_218280","gene_symbol":"TOM40","run_date":"2026-09-08T11:06:34","timeline":{"discoveries":[{"year":2016,"finding":"T. gondii TOM40 (TgTom40) is a component of the translocon of the outer mitochondrial membrane (TOM) complex, required for mitochondrial protein import and parasite survival, consistent with homologues identified across all major mitochondrial protein translocons in apicomplexans.","method":"Homologue identification and functional characterization of TOM complex components in T. gondii, with TgTom22 and TgTom7 used as direct experimental handles for TOM complex assembly and import assays","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — TgTom40 is identified as part of the TOM complex and its role inferred from complex characterization, but direct loss-of-function experiments in this paper focus on TgTom22 and TgTom7; TgTom40's role is established by complex membership rather than its own KO","pmids":["27458014"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2024,"finding":"TgTom40, a component of the mitochondrial TOM translocon, interacts with nuclear pore components and acts as a molecular tether at nuclear-mitochondrial membrane contact sites; genetic disruption of TgTom40 reduces these contact sites, demonstrating its role in mediating mitochondrial-nuclear membrane apposition.","method":"Genetic disruption (conditional depletion) of TgTom40 combined with quantitative imaging of membrane contact sites; co-interaction between nuclear pore (TgNup503) and TOM translocon components identified as molecular tethers","journal":"The Journal of cell biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — single lab, genetic disruption with direct morphological/contact site readout and interaction data, but full reciprocal Co-IP/structural validation not described in abstract","pmids":["38456969"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"current_model":"TgTom40 is a core component of the outer mitochondrial membrane TOM translocon in Toxoplasma gondii, essential for mitochondrial protein import, and additionally functions as a molecular tether at nuclear-mitochondrial membrane contact sites through interaction with nuclear pore components."},"narrative":{"mechanistic_narrative":"TgTom40 is a core component of the translocon of the outer mitochondrial membrane (TOM) complex in Toxoplasma gondii, where it is required for mitochondrial protein import and parasite survival [PMID:27458014]. Beyond its canonical import function, TgTom40 additionally serves as a molecular tether at nuclear-mitochondrial membrane contact sites: it interacts with nuclear pore components including TgNup503, and its genetic disruption reduces the abundance of these contact sites, establishing a role in mediating mitochondrial-nuclear membrane apposition [PMID:38456969]. No further mechanistic detail—including structural organization of the channel or a defined substrate repertoire—has been characterized in the available corpus.","teleology":[{"year":2016,"claim":"Establishing that apicomplexan mitochondria possess a conserved import machinery, this work identified TgTom40 as a component of the TOM complex required for mitochondrial protein import and parasite survival, defining the core import route in T. gondii.","evidence":"Homologue identification and functional characterization of TOM complex components, using TgTom22 and TgTom7 as experimental handles for complex assembly and import assays","pmids":["27458014"],"confidence":"Medium","gaps":["TgTom40's role is inferred from complex membership rather than its own loss-of-function experiment","No structural model of the TgTom40 channel","Substrate repertoire imported through the complex not defined"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2024,"claim":"Testing whether a mitochondrial import component has functions beyond translocation, this work showed TgTom40 acts as a molecular tether at nuclear-mitochondrial contact sites by interacting with nuclear pore components, revealing an inter-organelle scaffolding role.","evidence":"Conditional genetic depletion of TgTom40 with quantitative imaging of membrane contact sites, plus identification of co-interaction between nuclear pore (TgNup503) and TOM translocon components","pmids":["38456969"],"confidence":"Medium","gaps":["Full reciprocal Co-IP and structural validation of the tether interaction not described","Whether the tethering function is separable from the import function is unresolved","Functional consequence of contact-site loss for parasite physiology not established"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":null,"claim":"Whether TgTom40's import channel activity and its membrane-tethering role are mechanistically coupled, and how substrate selection and translocation occur at the molecular level, remain open.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No direct loss-of-function characterization of TgTom40 in the import context","No structural determination of the TOM channel in T. gondii","Mechanism coupling import and tethering functions unknown"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["TOM complex (translocon of the outer mitochondrial membrane), including TgTom22 and TgTom7"],"partners":["TGTOM22","TGTOM7","TGNUP503 (NUCLEAR PORE COMPONENT)"],"other_free_text":["Functions as a molecular tether at nuclear-mitochondrial membrane contact sites; genetic disruption reduces contact site abundance."]},"strain_conflicts":[]},"prefetch_data":{},"corpus_meta":[{"pmid":"27458014","id":"PMC_27458014","title":"The Import of Proteins into the Mitochondrion of Toxoplasma gondii.","date":"2016","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/27458014","citation_count":42,"is_preprint":false},{"pmid":"38456969","id":"PMC_38456969","title":"Two ancient membrane pores mediate mitochondrial-nucleus membrane contact sites.","date":"2024","source":"The Journal of cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/38456969","citation_count":13,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":3234,"output_tokens":666,"usd":0.009846,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5400,"output_tokens":1616,"usd":0.0337,"stage2_stop_reason":"end_turn"},"total_usd":0.043546,"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\": 2016,\n      \"finding\": \"T. gondii TOM40 (TgTom40) is a component of the translocon of the outer mitochondrial membrane (TOM) complex, required for mitochondrial protein import and parasite survival, consistent with homologues identified across all major mitochondrial protein translocons in apicomplexans.\",\n      \"method\": \"Homologue identification and functional characterization of TOM complex components in T. gondii, with TgTom22 and TgTom7 used as direct experimental handles for TOM complex assembly and import assays\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — TgTom40 is identified as part of the TOM complex and its role inferred from complex characterization, but direct loss-of-function experiments in this paper focus on TgTom22 and TgTom7; TgTom40's role is established by complex membership rather than its own KO\",\n      \"pmids\": [\"27458014\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"TgTom40, a component of the mitochondrial TOM translocon, interacts with nuclear pore components and acts as a molecular tether at nuclear-mitochondrial membrane contact sites; genetic disruption of TgTom40 reduces these contact sites, demonstrating its role in mediating mitochondrial-nuclear membrane apposition.\",\n      \"method\": \"Genetic disruption (conditional depletion) of TgTom40 combined with quantitative imaging of membrane contact sites; co-interaction between nuclear pore (TgNup503) and TOM translocon components identified as molecular tethers\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — single lab, genetic disruption with direct morphological/contact site readout and interaction data, but full reciprocal Co-IP/structural validation not described in abstract\",\n      \"pmids\": [\"38456969\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"TgTom40 is a core component of the outer mitochondrial membrane TOM translocon in Toxoplasma gondii, essential for mitochondrial protein import, and additionally functions as a molecular tether at nuclear-mitochondrial membrane contact sites through interaction with nuclear pore components.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"TgTom40 is a core component of the translocon of the outer mitochondrial membrane (TOM) complex in Toxoplasma gondii, where it is required for mitochondrial protein import and parasite survival [#0]. Beyond its canonical import function, TgTom40 additionally serves as a molecular tether at nuclear-mitochondrial membrane contact sites: it interacts with nuclear pore components including TgNup503, and its genetic disruption reduces the abundance of these contact sites, establishing a role in mediating mitochondrial-nuclear membrane apposition [#1]. No further mechanistic detail—including structural organization of the channel or a defined substrate repertoire—has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2016,\n      \"claim\": \"Establishing that apicomplexan mitochondria possess a conserved import machinery, this work identified TgTom40 as a component of the TOM complex required for mitochondrial protein import and parasite survival, defining the core import route in T. gondii.\",\n      \"evidence\": \"Homologue identification and functional characterization of TOM complex components, using TgTom22 and TgTom7 as experimental handles for complex assembly and import assays\",\n      \"pmids\": [\"27458014\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"TgTom40's role is inferred from complex membership rather than its own loss-of-function experiment\",\n        \"No structural model of the TgTom40 channel\",\n        \"Substrate repertoire imported through the complex not defined\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Testing whether a mitochondrial import component has functions beyond translocation, this work showed TgTom40 acts as a molecular tether at nuclear-mitochondrial contact sites by interacting with nuclear pore components, revealing an inter-organelle scaffolding role.\",\n      \"evidence\": \"Conditional genetic depletion of TgTom40 with quantitative imaging of membrane contact sites, plus identification of co-interaction between nuclear pore (TgNup503) and TOM translocon components\",\n      \"pmids\": [\"38456969\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Full reciprocal Co-IP and structural validation of the tether interaction not described\",\n        \"Whether the tethering function is separable from the import function is unresolved\",\n        \"Functional consequence of contact-site loss for parasite physiology not established\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Whether TgTom40's import channel activity and its membrane-tethering role are mechanistically coupled, and how substrate selection and translocation occur at the molecular level, remain open.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No direct loss-of-function characterization of TgTom40 in the import context\",\n        \"No structural determination of the TOM channel in T. gondii\",\n        \"Mechanism coupling import and tethering functions unknown\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0015450\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005741\", \"supporting_discovery_ids\": [0, 1], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]},\n      {\"term_id\": \"GO:0044233\", \"supporting_discovery_ids\": [1], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0006626\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"complexes\": [\n      \"TOM complex (translocon of the outer mitochondrial membrane), including TgTom22 and TgTom7\"\n    ],\n    \"partners\": [\n      \"TgTom22\",\n      \"TgTom7\",\n      \"TgNup503 (nuclear pore component)\"\n    ],\n    \"other_free_text\": [\n      \"Functions as a molecular tether at nuclear-mitochondrial membrane contact sites; genetic disruption reduces contact site abundance.\"\n    ]\n  },\n  \"strain_conflicts\": []\n}\n```","audit_flag":null,"strains":[{"strain":"ME49","gene_id":"TGME49_218280","name":"TOM40","product":"mitochondrial import receptor subunit TOM40","uniprot_acc":"A0A125YIH2","chromosome":"TGME49_chrXII","start_pos":1627626},{"strain":"GT1","gene_id":"TGGT1_218280","name":null,"product":"putative eukaryotic porin","uniprot_acc":null,"chromosome":"TGGT1_chrXII","start_pos":1568398},{"strain":"RH88","gene_id":"TGRH88_059070","name":null,"product":"putative eukaryotic porin","uniprot_acc":null,"chromosome":"CM023093","start_pos":1640187},{"strain":"VEG","gene_id":"TGVEG_218280","name":null,"product":"putative eukaryotic porin","uniprot_acc":"B6KRZ3","chromosome":"TGVEG_chrXII","start_pos":1601555}]}