{"gene":"TG_225800","gene_symbol":"SUFC","run_date":"2026-09-08T11:06:44","timeline":{"discoveries":[{"year":2022,"finding":"TgSUFC encodes an ATPase component of the plastidic SUF (sulfur utilization factor) iron-sulfur cluster biogenesis pathway in Toxoplasma gondii; conditional depletion of TgSUFC (alongside TgNFS2) causes severe, irreversible defects in parasite division and membrane homeostasis, demonstrating that TgSUFC is essential for iron-sulfur cluster assembly in the apicoplast.","method":"Conditional knockdown/depletion mutant generation with phenotypic analysis (division and membrane homeostasis readouts)","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean conditional KO with defined cellular phenotype (division arrest, membrane defects), single lab, multiple phenotypic readouts","pmids":["35810787"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2022,"finding":"Depletion of TgSUFC impairs apicoplast-generated fatty acid synthesis, as evidenced by lipid analysis, but exogenous fatty acid supplementation or increased host scavenging does not fully rescue parasite growth, indicating fatty acid deficiency is not the sole lethal consequence of disrupting the SUF pathway.","method":"Lipid/fatty acid analysis combined with exogenous fatty acid supplementation rescue experiments","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — functional rescue experiment combined with lipid analysis in a single lab study","pmids":["35810787"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2022,"finding":"TgSUFC depletion disrupts isoprenoid biosynthesis derived from the apicoplast, leading to defects in GPI-anchored protein targeting and parasite motility, placing the SUF pathway upstream of isoprenoid-dependent processes in Toxoplasma.","method":"Conditional knockdown with GPI-anchored protein localization assay and motility assay","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — loss-of-function with two defined downstream phenotypic readouts (GPI targeting, motility) in a single lab study","pmids":["35810787"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"current_model":"TgSUFC is an ATPase subunit of the apicoplast SUF iron-sulfur cluster assembly pathway in Toxoplasma gondii; its depletion irreversibly abolishes parasite division and membrane homeostasis by impairing iron-sulfur cluster biogenesis, which in turn disrupts apicoplast-generated fatty acid synthesis and isoprenoid-dependent processes including GPI-anchored protein targeting and parasite motility."},"narrative":{"mechanistic_narrative":"TgSUFC is an ATPase component of the plastidic SUF (sulfur utilization factor) iron-sulfur cluster biogenesis pathway operating in the apicoplast of Toxoplasma gondii, and it is essential for parasite division and membrane homeostasis [PMID:35810787]. Conditional depletion of TgSUFC causes severe, irreversible defects in parasite division and membrane integrity, establishing its requirement for iron-sulfur cluster assembly [PMID:35810787]. Because Fe-S cofactors feed downstream apicoplast metabolism, loss of TgSUFC impairs apicoplast-generated fatty acid synthesis, though exogenous fatty acid supplementation does not fully rescue growth, indicating fatty acid deficiency is not the sole lethal consequence [PMID:35810787]. TgSUFC depletion also disrupts apicoplast-derived isoprenoid biosynthesis, producing downstream defects in GPI-anchored protein targeting and parasite motility, and thereby placing the SUF pathway upstream of multiple isoprenoid-dependent processes [PMID:35810787]. Beyond these loss-of-function phenotypes, no structural, enzymatic, or interaction-level detail of TgSUFC has been characterized in the available corpus.","teleology":[{"year":2022,"claim":"Establishing whether the apicoplast SUF pathway is essential in Toxoplasma required a component-level test; conditional depletion of the ATPase subunit TgSUFC showed the pathway is indispensable for parasite division and membrane homeostasis.","evidence":"Conditional knockdown/depletion mutant with division and membrane homeostasis phenotyping in T. gondii","pmids":["35810787"],"confidence":"Medium","gaps":["No biochemical demonstration of TgSUFC ATPase activity or Fe-S cluster assembly in vitro","Direct interaction partners within the SUF machinery not mapped","No structural model of the TgSUFC subunit or complex"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2022,"claim":"To identify which downstream apicoplast function is compromised, lipid analysis and rescue experiments showed TgSUFC loss impairs fatty acid synthesis but that this deficiency alone does not explain lethality.","evidence":"Lipid/fatty acid analysis with exogenous fatty acid supplementation rescue in T. gondii","pmids":["35810787"],"confidence":"Medium","gaps":["The additional lethal consequences beyond fatty acid deficiency remain unresolved","Which specific Fe-S-dependent enzymes are inactivated is not defined"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2022,"claim":"To connect Fe-S biogenesis to broader parasite biology, phenotypic assays showed TgSUFC depletion disrupts apicoplast-derived isoprenoid biosynthesis, causing defects in GPI-anchored protein targeting and motility.","evidence":"Conditional knockdown with GPI-anchored protein localization and motility assays in T. gondii","pmids":["35810787"],"confidence":"Medium","gaps":["The specific isoprenoid-dependent enzyme(s) requiring Fe-S clusters are not identified","Causal chain from isoprenoid loss to GPI mistargeting not mechanistically dissected"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":null,"claim":"The biochemical activity of TgSUFC, its assembly into the SUF complex, and the direct Fe-S client enzymes that link the pathway to fatty acid and isoprenoid metabolism remain uncharacterized.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No in vitro reconstitution of TgSUFC ATPase or Fe-S cluster transfer activity","No structural or interaction data for the T. gondii SUF machinery","Identity of Fe-S-dependent target enzymes not established"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["Apicoplast SUF iron-sulfur cluster assembly machinery"],"partners":["TGNFS2"],"other_free_text":["Depletion causes irreversible defects in parasite division and membrane homeostasis [#0]","Required upstream of apicoplast fatty acid synthesis; fatty acid supplementation does not fully rescue [#1]","Required for isoprenoid-dependent GPI-anchored protein targeting and parasite motility [#2]"]},"strain_conflicts":[]},"prefetch_data":{},"corpus_meta":[{"pmid":"35810787","id":"PMC_35810787","title":"Disrupting the plastidic iron-sulfur cluster biogenesis pathway in Toxoplasma gondii has pleiotropic effects irreversibly impacting parasite viability.","date":"2022","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/35810787","citation_count":25,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":2988,"output_tokens":836,"usd":0.010752,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5718,"output_tokens":2217,"usd":0.042008,"stage2_stop_reason":"end_turn"},"total_usd":0.05276,"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\": 2022,\n      \"finding\": \"TgSUFC encodes an ATPase component of the plastidic SUF (sulfur utilization factor) iron-sulfur cluster biogenesis pathway in Toxoplasma gondii; conditional depletion of TgSUFC (alongside TgNFS2) causes severe, irreversible defects in parasite division and membrane homeostasis, demonstrating that TgSUFC is essential for iron-sulfur cluster assembly in the apicoplast.\",\n      \"method\": \"Conditional knockdown/depletion mutant generation with phenotypic analysis (division and membrane homeostasis readouts)\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean conditional KO with defined cellular phenotype (division arrest, membrane defects), single lab, multiple phenotypic readouts\",\n      \"pmids\": [\"35810787\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"Depletion of TgSUFC impairs apicoplast-generated fatty acid synthesis, as evidenced by lipid analysis, but exogenous fatty acid supplementation or increased host scavenging does not fully rescue parasite growth, indicating fatty acid deficiency is not the sole lethal consequence of disrupting the SUF pathway.\",\n      \"method\": \"Lipid/fatty acid analysis combined with exogenous fatty acid supplementation rescue experiments\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — functional rescue experiment combined with lipid analysis in a single lab study\",\n      \"pmids\": [\"35810787\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"TgSUFC depletion disrupts isoprenoid biosynthesis derived from the apicoplast, leading to defects in GPI-anchored protein targeting and parasite motility, placing the SUF pathway upstream of isoprenoid-dependent processes in Toxoplasma.\",\n      \"method\": \"Conditional knockdown with GPI-anchored protein localization assay and motility assay\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — loss-of-function with two defined downstream phenotypic readouts (GPI targeting, motility) in a single lab study\",\n      \"pmids\": [\"35810787\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"TgSUFC is an ATPase subunit of the apicoplast SUF iron-sulfur cluster assembly pathway in Toxoplasma gondii; its depletion irreversibly abolishes parasite division and membrane homeostasis by impairing iron-sulfur cluster biogenesis, which in turn disrupts apicoplast-generated fatty acid synthesis and isoprenoid-dependent processes including GPI-anchored protein targeting and parasite motility.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"TgSUFC is an ATPase component of the plastidic SUF (sulfur utilization factor) iron-sulfur cluster biogenesis pathway operating in the apicoplast of Toxoplasma gondii, and it is essential for parasite division and membrane homeostasis [#0]. Conditional depletion of TgSUFC causes severe, irreversible defects in parasite division and membrane integrity, establishing its requirement for iron-sulfur cluster assembly [#0]. Because Fe-S cofactors feed downstream apicoplast metabolism, loss of TgSUFC impairs apicoplast-generated fatty acid synthesis, though exogenous fatty acid supplementation does not fully rescue growth, indicating fatty acid deficiency is not the sole lethal consequence [#1]. TgSUFC depletion also disrupts apicoplast-derived isoprenoid biosynthesis, producing downstream defects in GPI-anchored protein targeting and parasite motility, and thereby placing the SUF pathway upstream of multiple isoprenoid-dependent processes [#2]. Beyond these loss-of-function phenotypes, no structural, enzymatic, or interaction-level detail of TgSUFC has been characterized in the available corpus.\"\n    ,\n  \"teleology\": [\n    {\n      \"year\": 2022,\n      \"claim\": \"Establishing whether the apicoplast SUF pathway is essential in Toxoplasma required a component-level test; conditional depletion of the ATPase subunit TgSUFC showed the pathway is indispensable for parasite division and membrane homeostasis.\",\n      \"evidence\": \"Conditional knockdown/depletion mutant with division and membrane homeostasis phenotyping in T. gondii\",\n      \"pmids\": [\"35810787\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No biochemical demonstration of TgSUFC ATPase activity or Fe-S cluster assembly in vitro\",\n        \"Direct interaction partners within the SUF machinery not mapped\",\n        \"No structural model of the TgSUFC subunit or complex\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"To identify which downstream apicoplast function is compromised, lipid analysis and rescue experiments showed TgSUFC loss impairs fatty acid synthesis but that this deficiency alone does not explain lethality.\",\n      \"evidence\": \"Lipid/fatty acid analysis with exogenous fatty acid supplementation rescue in T. gondii\",\n      \"pmids\": [\"35810787\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"The additional lethal consequences beyond fatty acid deficiency remain unresolved\",\n        \"Which specific Fe-S-dependent enzymes are inactivated is not defined\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"To connect Fe-S biogenesis to broader parasite biology, phenotypic assays showed TgSUFC depletion disrupts apicoplast-derived isoprenoid biosynthesis, causing defects in GPI-anchored protein targeting and motility.\",\n      \"evidence\": \"Conditional knockdown with GPI-anchored protein localization and motility assays in T. gondii\",\n      \"pmids\": [\"35810787\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"The specific isoprenoid-dependent enzyme(s) requiring Fe-S clusters are not identified\",\n        \"Causal chain from isoprenoid loss to GPI mistargeting not mechanistically dissected\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The biochemical activity of TgSUFC, its assembly into the SUF complex, and the direct Fe-S client enzymes that link the pathway to fatty acid and isoprenoid metabolism remain uncharacterized.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No in vitro reconstitution of TgSUFC ATPase or Fe-S cluster transfer activity\",\n        \"No structural or interaction data for the T. gondii SUF machinery\",\n        \"Identity of Fe-S-dependent target enzymes not established\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0016887\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]},\n      {\"term_id\": \"GO:0016226\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0009536\", \"supporting_discovery_ids\": [0, 1, 2], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0016226\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]},\n      {\"term_id\": \"GO:0006633\", \"supporting_discovery_ids\": [1], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]},\n      {\"term_id\": \"GO:0008299\", \"supporting_discovery_ids\": [2], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"complexes\": [\"Apicoplast SUF iron-sulfur cluster assembly machinery\"],\n    \"partners\": [\"TgNFS2\"],\n    \"other_free_text\": [\n      \"Depletion causes irreversible defects in parasite division and membrane homeostasis [#0]\",\n      \"Required upstream of apicoplast fatty acid synthesis; fatty acid supplementation does not fully rescue [#1]\",\n      \"Required for isoprenoid-dependent GPI-anchored protein targeting and parasite motility [#2]\"\n    ]\n  },\n  \"strain_conflicts\": []\n}\n```","audit_flag":null,"strains":[{"strain":"ME49","gene_id":"TGME49_225800","name":"SUFC","product":"iron-sulfur cluster assembly protein SufC","uniprot_acc":"S8F0T3","chromosome":"TGME49_chrX","start_pos":2031712},{"strain":"GT1","gene_id":"TGGT1_225800","name":null,"product":"iron-sulfur assembly ATPase","uniprot_acc":null,"chromosome":"TGGT1_chrX","start_pos":1940841},{"strain":"RH88","gene_id":"TGRH88_045430","name":null,"product":"iron-sulfur assembly ATPase","uniprot_acc":null,"chromosome":"CM023091","start_pos":5535073},{"strain":"VEG","gene_id":"TGVEG_225800","name":null,"product":"iron-sulfur assembly ATPase","uniprot_acc":"B9Q7V8","chromosome":"TGVEG_chrX","start_pos":1932586}]}