{"gene":"TG_263323","gene_symbol":"FIS1","run_date":"2026-09-08T14:08:29","timeline":{"discoveries":[{"year":2019,"finding":"The canonical fission adaptor TgFis1 is NOT required for mitochondrial fission in Toxoplasma gondii; instead, the divergent dynamin-related protein TgDrpC is essential for mitochondrial biogenesis and fission.","method":"Genetic depletion and dominant-negative expression of TgDrpC; functional assessment of TgFis1 by loss-of-function showing no fission defect","journal":"PLoS pathogens","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal genetic dissection of two proteins with defined organellar phenotypes; negative result for TgFis1 explicitly established by experiment, positive fission role for TgDrpC confirmed by two independent approaches (depletion and dominant-negative)","pmids":["30947298"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2020,"finding":"Mislocalization of endogenous Fis1 causes a dominant-negative effect on mitochondrial morphology, indicating that Fis1 interacts with proteins critical for maintaining mitochondrial structure.","method":"Endogenous protein mislocalization assay with mitochondrial morphology readout (dominant-negative effect)","journal":"mBio","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — single lab, dominant-negative localization experiment demonstrating functional interaction, but binding partners not directly identified for Fis1 itself","pmids":["32047127"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2020,"finding":"Fis1 function is required for monensin-induced reversible constriction of the mitochondrial outer membrane, placing Fis1 in the pathway of mitochondrial membrane remodeling in response to ionophore treatment.","method":"Monensin (ionophore) treatment combined with Fis1 functional perturbation; mitochondrial morphology readout","journal":"mBio","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — single lab, clean loss-of-function with defined morphological phenotype, but single method and no molecular mechanism detailed","pmids":["32047127"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2020,"finding":"Protein interaction trap screens using Fis1 as bait identified LMF1, a novel outer mitochondrial membrane protein essential for peripheral positioning of the mitochondrion (lasso morphology) in intracellular parasites.","method":"Protein interaction trap screens (pulldown/co-immunoprecipitation-based), followed by LMF1 loss-of-function with mitochondrial morphology and localization readouts","journal":"mBio","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — interaction identified by protein trap screens and validated functionally with loss-of-function; single lab but two orthogonal approaches (interaction screen + KO phenotype)","pmids":["32047127"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"current_model":"In Toxoplasma gondii, TgFis1 is not the canonical adaptor required for mitochondrial fission (that role belongs to TgDrpC), but Fis1 does participate in mitochondrial membrane remodeling and morphology maintenance, functioning through interactions with outer mitochondrial membrane proteins such as LMF1, which mediates peripheral (lasso-shaped) positioning of the mitochondrion at the parasite pellicle during intracellular growth."},"narrative":{"mechanistic_narrative":"In Toxoplasma gondii, TgFis1 is a mitochondrial outer membrane protein involved in mitochondrial morphology maintenance and membrane remodeling rather than in canonical organelle fission, which instead depends on the divergent dynamin-related protein TgDrpC [PMID:30947298]. Mislocalization of endogenous Fis1 exerts a dominant-negative effect on mitochondrial structure, indicating that Fis1 acts through interactions with proteins critical for maintaining mitochondrial architecture [PMID:32047127]. Fis1 is required for the reversible constriction of the mitochondrial outer membrane induced by the ionophore monensin, placing it in a membrane-remodeling pathway responsive to ionophore stress [PMID:32047127]. Interaction screens using Fis1 as bait identified LMF1, an outer mitochondrial membrane protein essential for the peripheral, lasso-shaped positioning of the mitochondrion in intracellular parasites [PMID:32047127]. Beyond these findings, the biochemical mechanism by which Fis1 contributes to membrane remodeling and positioning has not been characterized in the available corpus.","teleology":[{"year":2019,"claim":"Whether the canonical fission adaptor Fis1 drives mitochondrial fission in Toxoplasma was unknown; reciprocal genetic dissection established that TgFis1 is dispensable for fission and that the divergent dynamin-related protein TgDrpC carries this role.","evidence":"Genetic depletion and dominant-negative expression of TgDrpC alongside loss-of-function assessment of TgFis1, scored by organellar phenotype","pmids":["30947298"],"confidence":"High","gaps":["Does not define what Fis1 does if not fission","Molecular mechanism of TgDrpC recruitment not addressed"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2020,"claim":"Having excluded a fission role, the question became whether Fis1 has any structural function; mislocalization of endogenous Fis1 produced a dominant-negative mitochondrial morphology defect, showing Fis1 engages partners important for organelle architecture.","evidence":"Endogenous protein mislocalization assay with mitochondrial morphology readout","pmids":["32047127"],"confidence":"Medium","gaps":["Binding partners not directly identified in this experiment","Direct versus indirect effect on morphology not resolved"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2020,"claim":"To place Fis1 in a defined remodeling process, monensin-induced outer membrane constriction was tested and shown to require Fis1 function, embedding Fis1 in ionophore-responsive membrane remodeling.","evidence":"Monensin (ionophore) treatment combined with Fis1 functional perturbation and morphology readout","pmids":["32047127"],"confidence":"Medium","gaps":["Single method with no molecular mechanism","How Fis1 senses or transduces the ionophore signal is unknown"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2020,"claim":"To identify the partners through which Fis1 acts, interaction trap screens using Fis1 as bait recovered LMF1, an outer membrane protein required for peripheral lasso-shaped positioning of the mitochondrion in intracellular parasites.","evidence":"Protein interaction trap/pulldown screens with Fis1 bait, followed by LMF1 loss-of-function morphology and localization assays","pmids":["32047127"],"confidence":"Medium","gaps":["Direct Fis1-LMF1 binding interface not defined","Single lab; reciprocal validation of the interaction not described"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":null,"claim":"The biochemical activity of Fis1 and the mechanism by which it links to LMF1 to drive membrane remodeling and mitochondrial positioning remain undefined.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No structural model of Fis1 or the Fis1-LMF1 complex","Enzymatic or scaffolding activity of Fis1 undetermined","Signal driving peripheral positioning not established"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["LMF1"],"other_free_text":["TgFis1 is dispensable for mitochondrial fission in Toxoplasma; fission depends on the dynamin-related protein TgDrpC [#0].","Fis1 is required for monensin-induced reversible constriction of the mitochondrial outer membrane [#2].","Fis1 interacts with LMF1 to support peripheral lasso-shaped positioning of the mitochondrion in intracellular parasites [#3]."]},"strain_conflicts":[]},"prefetch_data":{},"corpus_meta":[{"pmid":"30947298","id":"PMC_30947298","title":"A unique dynamin-related protein is essential for mitochondrial fission in Toxoplasma gondii.","date":"2019","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/30947298","citation_count":33,"is_preprint":false},{"pmid":"32047127","id":"PMC_32047127","title":"Identification of Fis1 Interactors in Toxoplasma gondii Reveals a Novel Protein Required for Peripheral Distribution of the Mitochondrion.","date":"2020","source":"mBio","url":"https://pubmed.ncbi.nlm.nih.gov/32047127","citation_count":29,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":3639,"output_tokens":1059,"usd":0.013401,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5993,"output_tokens":2108,"usd":0.041333,"stage2_stop_reason":"end_turn"},"total_usd":0.054734,"stage1_batch_id":"msgbatch_015xmQKDRqnTh9anE4m7LiD6","stage2_batch_id":"msgbatch_01JLpkFTVhoQBNgqHCKFrVVU","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2019,\n      \"finding\": \"The canonical fission adaptor TgFis1 is NOT required for mitochondrial fission in Toxoplasma gondii; instead, the divergent dynamin-related protein TgDrpC is essential for mitochondrial biogenesis and fission.\",\n      \"method\": \"Genetic depletion and dominant-negative expression of TgDrpC; functional assessment of TgFis1 by loss-of-function showing no fission defect\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal genetic dissection of two proteins with defined organellar phenotypes; negative result for TgFis1 explicitly established by experiment, positive fission role for TgDrpC confirmed by two independent approaches (depletion and dominant-negative)\",\n      \"pmids\": [\"30947298\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"Mislocalization of endogenous Fis1 causes a dominant-negative effect on mitochondrial morphology, indicating that Fis1 interacts with proteins critical for maintaining mitochondrial structure.\",\n      \"method\": \"Endogenous protein mislocalization assay with mitochondrial morphology readout (dominant-negative effect)\",\n      \"journal\": \"mBio\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — single lab, dominant-negative localization experiment demonstrating functional interaction, but binding partners not directly identified for Fis1 itself\",\n      \"pmids\": [\"32047127\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"Fis1 function is required for monensin-induced reversible constriction of the mitochondrial outer membrane, placing Fis1 in the pathway of mitochondrial membrane remodeling in response to ionophore treatment.\",\n      \"method\": \"Monensin (ionophore) treatment combined with Fis1 functional perturbation; mitochondrial morphology readout\",\n      \"journal\": \"mBio\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — single lab, clean loss-of-function with defined morphological phenotype, but single method and no molecular mechanism detailed\",\n      \"pmids\": [\"32047127\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"Protein interaction trap screens using Fis1 as bait identified LMF1, a novel outer mitochondrial membrane protein essential for peripheral positioning of the mitochondrion (lasso morphology) in intracellular parasites.\",\n      \"method\": \"Protein interaction trap screens (pulldown/co-immunoprecipitation-based), followed by LMF1 loss-of-function with mitochondrial morphology and localization readouts\",\n      \"journal\": \"mBio\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — interaction identified by protein trap screens and validated functionally with loss-of-function; single lab but two orthogonal approaches (interaction screen + KO phenotype)\",\n      \"pmids\": [\"32047127\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"In Toxoplasma gondii, TgFis1 is not the canonical adaptor required for mitochondrial fission (that role belongs to TgDrpC), but Fis1 does participate in mitochondrial membrane remodeling and morphology maintenance, functioning through interactions with outer mitochondrial membrane proteins such as LMF1, which mediates peripheral (lasso-shaped) positioning of the mitochondrion at the parasite pellicle during intracellular growth.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"In Toxoplasma gondii, TgFis1 is a mitochondrial outer membrane protein involved in mitochondrial morphology maintenance and membrane remodeling rather than in canonical organelle fission, which instead depends on the divergent dynamin-related protein TgDrpC [#0]. Mislocalization of endogenous Fis1 exerts a dominant-negative effect on mitochondrial structure, indicating that Fis1 acts through interactions with proteins critical for maintaining mitochondrial architecture [#1]. Fis1 is required for the reversible constriction of the mitochondrial outer membrane induced by the ionophore monensin, placing it in a membrane-remodeling pathway responsive to ionophore stress [#2]. Interaction screens using Fis1 as bait identified LMF1, an outer mitochondrial membrane protein essential for the peripheral, lasso-shaped positioning of the mitochondrion in intracellular parasites [#3]. Beyond these findings, the biochemical mechanism by which Fis1 contributes to membrane remodeling and positioning has not been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2019,\n      \"claim\": \"Whether the canonical fission adaptor Fis1 drives mitochondrial fission in Toxoplasma was unknown; reciprocal genetic dissection established that TgFis1 is dispensable for fission and that the divergent dynamin-related protein TgDrpC carries this role.\",\n      \"evidence\": \"Genetic depletion and dominant-negative expression of TgDrpC alongside loss-of-function assessment of TgFis1, scored by organellar phenotype\",\n      \"pmids\": [\"30947298\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Does not define what Fis1 does if not fission\", \"Molecular mechanism of TgDrpC recruitment not addressed\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Having excluded a fission role, the question became whether Fis1 has any structural function; mislocalization of endogenous Fis1 produced a dominant-negative mitochondrial morphology defect, showing Fis1 engages partners important for organelle architecture.\",\n      \"evidence\": \"Endogenous protein mislocalization assay with mitochondrial morphology readout\",\n      \"pmids\": [\"32047127\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Binding partners not directly identified in this experiment\", \"Direct versus indirect effect on morphology not resolved\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"To place Fis1 in a defined remodeling process, monensin-induced outer membrane constriction was tested and shown to require Fis1 function, embedding Fis1 in ionophore-responsive membrane remodeling.\",\n      \"evidence\": \"Monensin (ionophore) treatment combined with Fis1 functional perturbation and morphology readout\",\n      \"pmids\": [\"32047127\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single method with no molecular mechanism\", \"How Fis1 senses or transduces the ionophore signal is unknown\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"To identify the partners through which Fis1 acts, interaction trap screens using Fis1 as bait recovered LMF1, an outer membrane protein required for peripheral lasso-shaped positioning of the mitochondrion in intracellular parasites.\",\n      \"evidence\": \"Protein interaction trap/pulldown screens with Fis1 bait, followed by LMF1 loss-of-function morphology and localization assays\",\n      \"pmids\": [\"32047127\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct Fis1-LMF1 binding interface not defined\", \"Single lab; reciprocal validation of the interaction not described\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The biochemical activity of Fis1 and the mechanism by which it links to LMF1 to drive membrane remodeling and mitochondrial positioning remain undefined.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No structural model of Fis1 or the Fis1-LMF1 complex\", \"Enzymatic or scaffolding activity of Fis1 undetermined\", \"Signal driving peripheral positioning not established\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0005515\", \"supporting_discovery_ids\": [3], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005741\", \"supporting_discovery_ids\": [3], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0007005\", \"supporting_discovery_ids\": [1, 2, 3], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"LMF1\"],\n    \"other_free_text\": [\n      \"TgFis1 is dispensable for mitochondrial fission in Toxoplasma; fission depends on the dynamin-related protein TgDrpC [#0].\",\n      \"Fis1 is required for monensin-induced reversible constriction of the mitochondrial outer membrane [#2].\",\n      \"Fis1 interacts with LMF1 to support peripheral lasso-shaped positioning of the mitochondrion in intracellular parasites [#3].\"\n    ]\n  },\n  \"strain_conflicts\": []\n}","audit_flag":null,"strains":[{"strain":"ME49","gene_id":"TGME49_263323","name":"FIS1","product":"mitochondrial fission 1 protein","uniprot_acc":"A0A125YHR3","chromosome":"TGME49_chrVIIb","start_pos":631506},{"strain":"GT1","gene_id":"TGGT1_263323","name":null,"product":"putative tetratricopeptide repeat protein 11","uniprot_acc":null,"chromosome":"TGGT1_chrVIIb","start_pos":606619},{"strain":"RH88","gene_id":"TGRH88_067680","name":null,"product":"putative tetratricopeptide repeat protein 11","uniprot_acc":null,"chromosome":"CM023089","start_pos":644873},{"strain":"VEG","gene_id":"TGVEG_263323","name":null,"product":"putative tetratricopeptide repeat protein 11","uniprot_acc":"A0A125YHR4","chromosome":"TGVEG_chrVIIb","start_pos":637711}]}