{"gene":"TG_230210","gene_symbol":"ALV12","run_date":"2026-09-10T21:09:19","timeline":{"discoveries":[{"year":2022,"finding":"IMC10 (ALV12) localizes at the inner membrane complex (IMC) and physically interacts with the outer mitochondrial membrane-associated protein LMF1, as confirmed by protein-protein interaction assays (including yeast two-hybrid screen); this interaction defines a novel membrane tether between the mitochondrion and the IMC in Toxoplasma.","method":"Yeast two-hybrid screen; protein-protein interaction assays (pulldown/Co-IP confirmation)","journal":"Journal of cell science","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal interaction confirmed by two orthogonal methods (Y2H + PPI assay), single lab","pmids":["36314270"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2022,"finding":"Conditional knockdown of IMC10 (ALV12) does not affect parasite viability but severely disrupts mitochondrial morphology in intracellular parasites and impairs mitochondrial distribution to daughter cells during division, phenocopying disruption of LMF1.","method":"Conditional knockdown (inducible knockdown system); live/fluorescence imaging of mitochondrial morphology and inheritance","journal":"Journal of cell science","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean conditional KO with defined cellular phenotype, single lab, orthogonal phenotypic readouts","pmids":["36314270"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2024,"finding":"The LMF1/IMC10 (ALV12) tethering complex is part of the machinery governing mitochondrial morphology and inheritance; in parasites lacking IMC10, mitochondrial morphology is defective and inheritance to daughter buds is impaired.","method":"Genetic disruption (conditional knockdown); ultrastructure expansion microscopy (U-ExM); fluorescence imaging","journal":"PLoS pathogens","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — loss-of-function with defined cellular phenotype, corroborated by prior publication, single lab","pmids":["39374269"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"current_model":"ALV12 (IMC10) is an alveolin-domain inner membrane complex protein that physically interacts with the outer mitochondrial membrane protein LMF1 to form a pellicle–mitochondrion tether; conditional depletion of IMC10 severely disrupts mitochondrial morphology and inheritance to daughter cells without affecting parasite viability, and IMC10 is among the earliest alveolins incorporated into forming daughter buds during division."},"narrative":{"mechanistic_narrative":"ALV12 (IMC10) is an alveolin-domain protein of the Toxoplasma gondii inner membrane complex (IMC) that functions as a structural tether coordinating mitochondrial morphology and inheritance with the parasite pellicle [PMID:36314270]. IMC10 localizes to the IMC and physically interacts with the outer mitochondrial membrane-associated protein LMF1, and this interaction defines a membrane tether linking the mitochondrion to the IMC [PMID:36314270]. Conditional depletion of IMC10 does not compromise parasite viability but severely disrupts mitochondrial morphology and impairs distribution of the mitochondrion to daughter cells during division, phenocopying loss of its partner LMF1 and establishing the LMF1/IMC10 complex as part of the machinery governing mitochondrial inheritance [PMID:36314270, PMID:39374269]. Beyond its role in this tethering complex, nothing further about ALV12 has been characterized in the available corpus.","teleology":[{"year":2022,"claim":"Identified how the Toxoplasma mitochondrion is physically anchored to the pellicle by establishing ALV12/IMC10 as an IMC-resident binding partner of the outer mitochondrial membrane protein LMF1, defining a novel mitochondrion-IMC tether.","evidence":"Yeast two-hybrid screen with orthogonal pulldown/Co-IP confirmation in T. gondii","pmids":["36314270"],"confidence":"Medium","gaps":["Interaction interface / alveolin domain requirement not mapped","Whether the interaction is direct or bridged by additional factors not resolved"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2022,"claim":"Tested the functional consequence of the tether by showing that conditional loss of ALV12/IMC10 disrupts mitochondrial morphology and inheritance without killing the parasite, establishing the tether as required for mitochondrial positioning rather than for survival.","evidence":"Inducible conditional knockdown with fluorescence imaging of mitochondrial morphology and inheritance in T. gondii","pmids":["36314270"],"confidence":"Medium","gaps":["Molecular mechanism linking tether loss to morphology defect unresolved","Residual mitochondrial function in depleted parasites not quantified"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2024,"claim":"Corroborated the LMF1/IMC10 complex as part of the machinery governing mitochondrial morphology and inheritance, with high-resolution imaging confirming defective inheritance to daughter buds upon IMC10 loss.","evidence":"Conditional knockdown plus ultrastructure expansion microscopy (U-ExM) and fluorescence imaging in T. gondii","pmids":["39374269"],"confidence":"Medium","gaps":["Full protein composition of the tethering machinery not defined","Spatiotemporal regulation of tether assembly during division not resolved"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["LMF1/IMC10 mitochondrion-IMC tethering complex"],"partners":["LMF1 (OUTER MITOCHONDRIAL MEMBRANE-ASSOCIATED PROTEIN)"],"other_free_text":["Alveolin-domain inner membrane complex protein; loaded onto forming daughter buds earlier than IMC1 and IMC4 during endodyogeny [#3].","Conditional depletion disrupts mitochondrial morphology and inheritance without affecting parasite viability [#1, #2]."]},"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":"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},{"pmid":"40501855","id":"PMC_40501855","title":"Toxoplasma IMC1 is a central component of the subpellicular network and plays critical roles in parasite morphology, replication, and infectivity.","date":"2025","source":"bioRxiv : the preprint server for biology","url":"https://pubmed.ncbi.nlm.nih.gov/40501855","citation_count":0,"is_preprint":false},{"pmid":"42113865","id":"PMC_42113865","title":"Toxoplasma IMC1 is a central component of the subpellicular network and plays critical roles in parasite morphology, replication, and infectivity.","date":"2026","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/42113865","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":2452,"output_tokens":34,"usd":0.003933,"stage1_stop_reason":"end_turn"},"stage2":{"model":"","input_tokens":0,"output_tokens":0,"usd":0.0},"total_usd":0.061665,"stage1_batch_id":"msgbatch_01WgHz6kceqm573AGLyz57at","stage2_batch_id":"msgbatch_01LK4wDYj5zYquahv7gi9893","note":"batch pricing = 50% of standard","corrective_rerun":"2026-09-10 wrong-gene rerun (round-4 rules)","corrective_reason":"re-read with subject anchor"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2022,\n      \"finding\": \"IMC10 (ALV12) localizes at the inner membrane complex (IMC) and physically interacts with the outer mitochondrial membrane-associated protein LMF1, as confirmed by protein-protein interaction assays (including yeast two-hybrid screen); this interaction defines a novel membrane tether between the mitochondrion and the IMC in Toxoplasma.\",\n      \"method\": \"Yeast two-hybrid screen; protein-protein interaction assays (pulldown/Co-IP confirmation)\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal interaction confirmed by two orthogonal methods (Y2H + PPI assay), single lab\",\n      \"pmids\": [\"36314270\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"Conditional knockdown of IMC10 (ALV12) does not affect parasite viability but severely disrupts mitochondrial morphology in intracellular parasites and impairs mitochondrial distribution to daughter cells during division, phenocopying disruption of LMF1.\",\n      \"method\": \"Conditional knockdown (inducible knockdown system); live/fluorescence imaging of mitochondrial morphology and inheritance\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean conditional KO with defined cellular phenotype, single lab, orthogonal phenotypic readouts\",\n      \"pmids\": [\"36314270\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"The LMF1/IMC10 (ALV12) tethering complex is part of the machinery governing mitochondrial morphology and inheritance; in parasites lacking IMC10, mitochondrial morphology is defective and inheritance to daughter buds is impaired.\",\n      \"method\": \"Genetic disruption (conditional knockdown); ultrastructure expansion microscopy (U-ExM); fluorescence imaging\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — loss-of-function with defined cellular phenotype, corroborated by prior publication, single lab\",\n      \"pmids\": [\"39374269\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"IMC10 (ALV12) is among the key alveolins loaded onto forming daughter buds at an earlier stage than IMC1 and IMC4 during daughter bud formation, placing IMC10 in the temporal hierarchy of IMC cytoskeletal assembly.\",\n      \"method\": \"Fluorescence microscopy (expression timing during endodyogeny); comparative analysis with other alveolins\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, single microscopy method, IMC10 mentioned comparatively in context of IMC1 study\",\n      \"pmids\": [\"40501855\"],\n      \"is_preprint\": true,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"ALV12 (IMC10) is an alveolin-domain inner membrane complex protein that physically interacts with the outer mitochondrial membrane protein LMF1 to form a pellicle–mitochondrion tether; conditional depletion of IMC10 severely disrupts mitochondrial morphology and inheritance to daughter cells without affecting parasite viability, and IMC10 is among the earliest alveolins incorporated into forming daughter buds during division.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"ALV12 (IMC10) is an alveolin-domain protein of the Toxoplasma gondii inner membrane complex (IMC) that functions as a structural tether coordinating mitochondrial morphology and inheritance with the parasite pellicle [#0, #1]. IMC10 localizes to the IMC and physically interacts with the outer mitochondrial membrane-associated protein LMF1, and this interaction defines a membrane tether linking the mitochondrion to the IMC [#0]. Conditional depletion of IMC10 does not compromise parasite viability but severely disrupts mitochondrial morphology and impairs distribution of the mitochondrion to daughter cells during division, phenocopying loss of its partner LMF1 and establishing the LMF1/IMC10 complex as part of the machinery governing mitochondrial inheritance [#1, #2]. Beyond its role in this tethering complex, nothing further about ALV12 has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2022,\n      \"claim\": \"Identified how the Toxoplasma mitochondrion is physically anchored to the pellicle by establishing ALV12/IMC10 as an IMC-resident binding partner of the outer mitochondrial membrane protein LMF1, defining a novel mitochondrion-IMC tether.\",\n      \"evidence\": \"Yeast two-hybrid screen with orthogonal pulldown/Co-IP confirmation in T. gondii\",\n      \"pmids\": [\"36314270\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Interaction interface / alveolin domain requirement not mapped\", \"Whether the interaction is direct or bridged by additional factors not resolved\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Tested the functional consequence of the tether by showing that conditional loss of ALV12/IMC10 disrupts mitochondrial morphology and inheritance without killing the parasite, establishing the tether as required for mitochondrial positioning rather than for survival.\",\n      \"evidence\": \"Inducible conditional knockdown with fluorescence imaging of mitochondrial morphology and inheritance in T. gondii\",\n      \"pmids\": [\"36314270\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Molecular mechanism linking tether loss to morphology defect unresolved\", \"Residual mitochondrial function in depleted parasites not quantified\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Corroborated the LMF1/IMC10 complex as part of the machinery governing mitochondrial morphology and inheritance, with high-resolution imaging confirming defective inheritance to daughter buds upon IMC10 loss.\",\n      \"evidence\": \"Conditional knockdown plus ultrastructure expansion microscopy (U-ExM) and fluorescence imaging in T. gondii\",\n      \"pmids\": [\"39374269\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Full protein composition of the tethering machinery not defined\", \"Spatiotemporal regulation of tether assembly during division not resolved\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Placed IMC10 in the temporal hierarchy of IMC cytoskeletal assembly by showing it is loaded onto forming daughter buds earlier than IMC1 and IMC4.\",\n      \"evidence\": \"Fluorescence microscopy of expression timing during endodyogeny, comparative with other alveolins in T. gondii (preprint)\",\n      \"pmids\": [\"40501855\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Single-lab, single-method observation reported comparatively within an IMC1 study; not independently confirmed\", \"Mechanistic significance of early loading for tether function not established\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How the alveolin domain of IMC10 mediates LMF1 binding and how tether assembly is coordinated with mitochondrial fission and daughter cell segregation remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No structural model of the IMC10-LMF1 interface\", \"Directness of the interaction unproven\", \"Link between assembly timing and tether function unknown\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0005515\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0070258\", \"supporting_discovery_ids\": [0, 3], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0000001\", \"supporting_discovery_ids\": [1, 2], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"complexes\": [\"LMF1/IMC10 mitochondrion-IMC tethering complex\"],\n    \"partners\": [\"LMF1 (outer mitochondrial membrane-associated protein)\"],\n    \"other_free_text\": [\n      \"Alveolin-domain inner membrane complex protein; loaded onto forming daughter buds earlier than IMC1 and IMC4 during endodyogeny [#3].\",\n      \"Conditional depletion disrupts mitochondrial morphology and inheritance without affecting parasite viability [#1, #2].\"\n    ]\n  },\n  \"strain_conflicts\": []\n}\n```","audit_flag":null,"strains":[{"strain":"ME49","gene_id":"TGME49_230210","name":"ALV12","product":"alveolin domain containing intermediate filament IMC10","uniprot_acc":"A0A125YHT9","chromosome":"TGME49_chrVIII","start_pos":685013},{"strain":"GT1","gene_id":"TGGT1_230210","name":null,"product":"alveolin domain containing intermediate filament IMC10","uniprot_acc":null,"chromosome":"TGGT1_chrVIII","start_pos":682439},{"strain":"RH88","gene_id":"TGRH88_074710","name":null,"product":"alveolin domain containing intermediate filament IMC10","uniprot_acc":null,"chromosome":"CM023089","start_pos":5792716},{"strain":"VEG","gene_id":"TGVEG_230210","name":null,"product":"alveolin domain containing intermediate filament IMC10","uniprot_acc":"B6KJB9","chromosome":"TGVEG_chrVIII","start_pos":692086}]}