{"gene":"TG_265180","gene_symbol":"LMF1","run_date":"2026-09-08T14:08:29","timeline":{"discoveries":[{"year":2020,"finding":"LMF1 is a novel outer mitochondrial membrane protein essential for peripheral positioning of the mitochondrion in intracellular Toxoplasma gondii parasites. Loss of LMF1 causes the mitochondrion to retract from the pellicle and collapse (as seen in extracellular parasites), associated with defects in parasite fitness and mitochondrial segregation.","method":"Protein interaction trap screens (identifying LMF1 as Fis1 interactor); conditional loss-of-function with mitochondrial morphology and division phenotype readouts; subcellular fractionation/localization","journal":"mBio","confidence":"High","confidence_rationale":"Tier 2 / Moderate — protein interaction screen identified LMF1, KO/knockdown with defined morphological and fitness phenotypes, localization to outer mitochondrial membrane, single lab with multiple orthogonal methods","pmids":["32047127"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2022,"finding":"LMF1 interacts with the inner membrane complex (IMC) protein IMC10 as confirmed by protein-protein interaction assays, forming a membrane tether between the mitochondrion outer membrane and the parasite pellicle (IMC). Conditional knockdown of IMC10 phenocopies LMF1 disruption, causing loss of lasso-shaped mitochondrial morphology and defects in mitochondrial distribution to daughter cells during division.","method":"Yeast two-hybrid screen for LMF1 interactors; protein-protein interaction assays confirming LMF1–IMC10 interaction; conditional knockdown of IMC10 with mitochondrial morphology and division phenotype readouts","journal":"Journal of cell science","confidence":"High","confidence_rationale":"Tier 2 / Moderate — reciprocal protein interaction assays plus genetic epistasis (IMC10 KD phenocopies LMF1 loss), single lab with multiple orthogonal methods","pmids":["36314270"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2024,"finding":"Mitochondrion vesicles extracted from parasites lacking LMF1 pull down less actin than those from wild-type parasites, indicating that LMF1 is important for the interaction between the mitochondrion and actin filaments. Additionally, Myosin A (MyoA), a putative LMF1 interactor identified by yeast two-hybrid, accumulates around the mitochondrion in late stages of division and is required for mitochondrial morphology and inheritance.","method":"Mitochondrion vesicle pulldown with actin filaments from LMF1-null vs. wild-type parasites; ultrastructure expansion microscopy (U-ExM) for MyoA localization; conditional loss-of-function of MyoA with mitochondrial morphology and inheritance phenotype readouts; actin network disruption experiments","journal":"PLoS pathogens","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — in vitro pulldown with mitochondrion vesicles, U-ExM localization, and KO phenotype, single lab with multiple methods but each individual result from a single study","pmids":["39374269"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"current_model":"LMF1 is an outer mitochondrial membrane protein in Toxoplasma gondii that tethers the mitochondrion to the parasite pellicle by interacting with the IMC protein IMC10, maintaining the lasso-shaped peripheral mitochondrial morphology during intracellular growth, facilitating mitochondrial segregation to daughter cells during division, and promoting mitochondrion–actin interaction (likely via Myosin A) required for organellar inheritance."},"narrative":{"mechanistic_narrative":"LMF1 (Lasso Maintenance Factor 1) is an outer mitochondrial membrane protein in Toxoplasma gondii that tethers the mitochondrion to the parasite pellicle to maintain its characteristic lasso-shaped peripheral morphology and ensure faithful organellar inheritance during intracellular division [PMID:32047127]. LMF1, originally identified as a Fis1 interactor, is required for the mitochondrion to remain apposed to the pellicle; its loss causes the organelle to retract and collapse and impairs parasite fitness and mitochondrial segregation [PMID:32047127]. LMF1 bridges the outer membrane to the inner membrane complex (IMC) by binding the IMC protein IMC10, and conditional knockdown of IMC10 phenocopies LMF1 disruption, establishing this interaction as the physical tether underlying lasso morphology and daughter-cell distribution [PMID:36314270]. LMF1 further promotes the association of the mitochondrion with the actin cytoskeleton—mitochondrial vesicles from LMF1-null parasites bind less actin—and the putative LMF1 interactor Myosin A accumulates around the dividing mitochondrion and is itself required for mitochondrial morphology and inheritance [PMID:39374269].","teleology":[{"year":2020,"claim":"Establishing how the Toxoplasma mitochondrion maintains its peripheral lasso morphology, LMF1 was identified as an outer membrane factor whose loss causes the organelle to retract from the pellicle and collapse, linking morphology to segregation and fitness.","evidence":"Protein interaction trap screen (Fis1 interactor), conditional loss-of-function with mitochondrial morphology/division readouts, and subcellular fractionation in T. gondii","pmids":["32047127"],"confidence":"High","gaps":["Did not identify the pellicle-side partner mediating tethering","Molecular basis of the actin/cytoskeletal contribution not addressed"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2022,"claim":"Defining the physical bridge between mitochondrion and pellicle, LMF1 was shown to bind the IMC protein IMC10, and IMC10 knockdown phenocopied LMF1 loss, establishing an outer-membrane-to-IMC tether responsible for lasso morphology and daughter-cell distribution.","evidence":"Yeast two-hybrid screen and protein-protein interaction assays confirming LMF1–IMC10 binding, plus conditional IMC10 knockdown with morphology/division phenotypes in T. gondii","pmids":["36314270"],"confidence":"High","gaps":["Structural basis and stoichiometry of the LMF1–IMC10 interface unresolved","Whether additional pellicle proteins participate in the tether not determined"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2024,"claim":"Connecting the tether to the cytoskeleton, LMF1 was shown to promote mitochondrion–actin interaction and to associate with Myosin A, which localizes around the dividing mitochondrion and is required for its morphology and inheritance, implicating an actomyosin-based mechanism in organellar segregation.","evidence":"Mitochondrion-vesicle actin pulldowns from LMF1-null vs. wild-type parasites, U-ExM MyoA localization, MyoA conditional loss-of-function, and actin network disruption in T. gondii","pmids":["39374269"],"confidence":"Medium","gaps":["Direct binding between LMF1 and MyoA (yeast two-hybrid candidate) not biochemically confirmed","Whether the actin interaction is direct or bridged by intermediate factors is unresolved","Mechanistic order relative to the IMC10 tether during division not established"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":null,"claim":"How LMF1 coordinates the static IMC10 tether with dynamic actomyosin-driven segregation, and the molecular architecture of the full tethering complex, remain open.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No structural model of the LMF1 tethering complex","Direct versus indirect nature of LMF1–actin and LMF1–MyoA interactions unresolved","Regulation of tether assembly/disassembly across the division cycle uncharacterized"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["LMF1–IMC10 mitochondrion–pellicle tether"],"partners":["FIS1","IMC10","MYOSIN A (MYOA)","ACTIN FILAMENTS"],"other_free_text":["Tethers the outer mitochondrial membrane to the inner membrane complex (pellicle) to maintain lasso-shaped peripheral mitochondrial morphology in intracellular T. gondii.","Loss of LMF1 causes mitochondrial retraction/collapse, reduced parasite fitness, and defective mitochondrial segregation to daughter cells.","Promotes mitochondrion–actin interaction and associates with MyoA, implicating actomyosin in mitochondrial inheritance."]},"strain_conflicts":[]},"prefetch_data":{},"corpus_meta":[{"pmid":"36314270","id":"PMC_36314270","title":"IMC10 and LMF1 mediate mitochondrial morphology through mitochondrion-pellicle contact sites in Toxoplasma gondii.","date":"2022","source":"Journal of cell science","url":"https://pubmed.ncbi.nlm.nih.gov/36314270","citation_count":35,"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},{"pmid":"39374269","id":"PMC_39374269","title":"Myosin A and F-Actin play a critical role in mitochondrial dynamics and inheritance in Toxoplasma gondii.","date":"2024","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/39374269","citation_count":4,"is_preprint":false},{"pmid":"38562694","id":"PMC_38562694","title":"Myosin A and F-Actin play a critical role in mitochondrial dynamics and inheritance in Toxoplasma gondii.","date":"2024","source":"bioRxiv : the preprint server for biology","url":"https://pubmed.ncbi.nlm.nih.gov/38562694","citation_count":1,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":4703,"output_tokens":1070,"usd":0.015079,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6004,"output_tokens":2412,"usd":0.04516,"stage2_stop_reason":"end_turn"},"total_usd":0.060239,"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\": 2020,\n      \"finding\": \"LMF1 is a novel outer mitochondrial membrane protein essential for peripheral positioning of the mitochondrion in intracellular Toxoplasma gondii parasites. Loss of LMF1 causes the mitochondrion to retract from the pellicle and collapse (as seen in extracellular parasites), associated with defects in parasite fitness and mitochondrial segregation.\",\n      \"method\": \"Protein interaction trap screens (identifying LMF1 as Fis1 interactor); conditional loss-of-function with mitochondrial morphology and division phenotype readouts; subcellular fractionation/localization\",\n      \"journal\": \"mBio\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — protein interaction screen identified LMF1, KO/knockdown with defined morphological and fitness phenotypes, localization to outer mitochondrial membrane, single lab with multiple orthogonal methods\",\n      \"pmids\": [\"32047127\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"LMF1 interacts with the inner membrane complex (IMC) protein IMC10 as confirmed by protein-protein interaction assays, forming a membrane tether between the mitochondrion outer membrane and the parasite pellicle (IMC). Conditional knockdown of IMC10 phenocopies LMF1 disruption, causing loss of lasso-shaped mitochondrial morphology and defects in mitochondrial distribution to daughter cells during division.\",\n      \"method\": \"Yeast two-hybrid screen for LMF1 interactors; protein-protein interaction assays confirming LMF1–IMC10 interaction; conditional knockdown of IMC10 with mitochondrial morphology and division phenotype readouts\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal protein interaction assays plus genetic epistasis (IMC10 KD phenocopies LMF1 loss), single lab with multiple orthogonal methods\",\n      \"pmids\": [\"36314270\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"Mitochondrion vesicles extracted from parasites lacking LMF1 pull down less actin than those from wild-type parasites, indicating that LMF1 is important for the interaction between the mitochondrion and actin filaments. Additionally, Myosin A (MyoA), a putative LMF1 interactor identified by yeast two-hybrid, accumulates around the mitochondrion in late stages of division and is required for mitochondrial morphology and inheritance.\",\n      \"method\": \"Mitochondrion vesicle pulldown with actin filaments from LMF1-null vs. wild-type parasites; ultrastructure expansion microscopy (U-ExM) for MyoA localization; conditional loss-of-function of MyoA with mitochondrial morphology and inheritance phenotype readouts; actin network disruption experiments\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — in vitro pulldown with mitochondrion vesicles, U-ExM localization, and KO phenotype, single lab with multiple methods but each individual result from a single study\",\n      \"pmids\": [\"39374269\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"LMF1 is an outer mitochondrial membrane protein in Toxoplasma gondii that tethers the mitochondrion to the parasite pellicle by interacting with the IMC protein IMC10, maintaining the lasso-shaped peripheral mitochondrial morphology during intracellular growth, facilitating mitochondrial segregation to daughter cells during division, and promoting mitochondrion–actin interaction (likely via Myosin A) required for organellar inheritance.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"LMF1 (Lasso Maintenance Factor 1) is an outer mitochondrial membrane protein in Toxoplasma gondii that tethers the mitochondrion to the parasite pellicle to maintain its characteristic lasso-shaped peripheral morphology and ensure faithful organellar inheritance during intracellular division [#0]. LMF1, originally identified as a Fis1 interactor, is required for the mitochondrion to remain apposed to the pellicle; its loss causes the organelle to retract and collapse and impairs parasite fitness and mitochondrial segregation [#0]. LMF1 bridges the outer membrane to the inner membrane complex (IMC) by binding the IMC protein IMC10, and conditional knockdown of IMC10 phenocopies LMF1 disruption, establishing this interaction as the physical tether underlying lasso morphology and daughter-cell distribution [#1]. LMF1 further promotes the association of the mitochondrion with the actin cytoskeleton\\u2014mitochondrial vesicles from LMF1-null parasites bind less actin\\u2014and the putative LMF1 interactor Myosin A accumulates around the dividing mitochondrion and is itself required for mitochondrial morphology and inheritance [#2].\",\n  \"teleology\": [\n    {\n      \"year\": 2020,\n      \"claim\": \"Establishing how the Toxoplasma mitochondrion maintains its peripheral lasso morphology, LMF1 was identified as an outer membrane factor whose loss causes the organelle to retract from the pellicle and collapse, linking morphology to segregation and fitness.\",\n      \"evidence\": \"Protein interaction trap screen (Fis1 interactor), conditional loss-of-function with mitochondrial morphology/division readouts, and subcellular fractionation in T. gondii\",\n      \"pmids\": [\"32047127\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Did not identify the pellicle-side partner mediating tethering\",\n        \"Molecular basis of the actin/cytoskeletal contribution not addressed\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Defining the physical bridge between mitochondrion and pellicle, LMF1 was shown to bind the IMC protein IMC10, and IMC10 knockdown phenocopied LMF1 loss, establishing an outer-membrane-to-IMC tether responsible for lasso morphology and daughter-cell distribution.\",\n      \"evidence\": \"Yeast two-hybrid screen and protein-protein interaction assays confirming LMF1\\u2013IMC10 binding, plus conditional IMC10 knockdown with morphology/division phenotypes in T. gondii\",\n      \"pmids\": [\"36314270\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Structural basis and stoichiometry of the LMF1\\u2013IMC10 interface unresolved\",\n        \"Whether additional pellicle proteins participate in the tether not determined\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Connecting the tether to the cytoskeleton, LMF1 was shown to promote mitochondrion\\u2013actin interaction and to associate with Myosin A, which localizes around the dividing mitochondrion and is required for its morphology and inheritance, implicating an actomyosin-based mechanism in organellar segregation.\",\n      \"evidence\": \"Mitochondrion-vesicle actin pulldowns from LMF1-null vs. wild-type parasites, U-ExM MyoA localization, MyoA conditional loss-of-function, and actin network disruption in T. gondii\",\n      \"pmids\": [\"39374269\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Direct binding between LMF1 and MyoA (yeast two-hybrid candidate) not biochemically confirmed\",\n        \"Whether the actin interaction is direct or bridged by intermediate factors is unresolved\",\n        \"Mechanistic order relative to the IMC10 tether during division not established\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How LMF1 coordinates the static IMC10 tether with dynamic actomyosin-driven segregation, and the molecular architecture of the full tethering complex, remain open.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No structural model of the LMF1 tethering complex\",\n        \"Direct versus indirect nature of LMF1\\u2013actin and LMF1\\u2013MyoA interactions unresolved\",\n        \"Regulation of tether assembly/disassembly across the division cycle uncharacterized\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0005515\", \"supporting_discovery_ids\": [0, 1, 2], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]},\n      {\"term_id\": \"GO:0051880\", \"supporting_discovery_ids\": [2], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005741\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0007005\", \"supporting_discovery_ids\": [0, 1], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]},\n      {\"term_id\": \"GO:0048311\", \"supporting_discovery_ids\": [0, 1, 2], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"complexes\": [\n      \"LMF1\\u2013IMC10 mitochondrion\\u2013pellicle tether\"\n    ],\n    \"partners\": [\n      \"Fis1\",\n      \"IMC10\",\n      \"Myosin A (MyoA)\",\n      \"actin filaments\"\n    ],\n    \"other_free_text\": [\n      \"Tethers the outer mitochondrial membrane to the inner membrane complex (pellicle) to maintain lasso-shaped peripheral mitochondrial morphology in intracellular T. gondii.\",\n      \"Loss of LMF1 causes mitochondrial retraction/collapse, reduced parasite fitness, and defective mitochondrial segregation to daughter cells.\",\n      \"Promotes mitochondrion\\u2013actin interaction and associates with MyoA, implicating actomyosin in mitochondrial inheritance.\"\n    ]\n  },\n  \"strain_conflicts\": []\n}","audit_flag":null,"strains":[{"strain":"ME49","gene_id":"TGME49_265180","name":"LMF1","product":"lasso maintenance factor LMF1","uniprot_acc":"A0A125YTR6","chromosome":"TGME49_chrIX","start_pos":1727137},{"strain":"GT1","gene_id":"TGGT1_265180","name":null,"product":"hypothetical protein","uniprot_acc":null,"chromosome":"TGGT1_chrIX","start_pos":1546295},{"strain":"RH88","gene_id":"TGRH88_012280","name":null,"product":"unspecified product","uniprot_acc":null,"chromosome":"CM023090","start_pos":1784933},{"strain":"VEG","gene_id":"TGVEG_265180","name":null,"product":"hypothetical protein","uniprot_acc":"B9QES7","chromosome":"TGVEG_chrIX","start_pos":1756046}]}