{"id":"d09a4c41-f1c5-5ac4-908d-14f8656c8419","stable_key":"434e1e27-eb90-583a-956b-62472726ffba:ca-micu1-occlusion-evidence","predicate":"inhibits","statement":"Purified MICU1 suppresses MCU-complex currents in patch-clamp experiments, and disruption of its MCU-interacting K126 residue abolishes this suppression.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"5784f3c6-42da-5cdf-96d8-fe5c09b28a1a","mechanism_event_label":"A later study directly observes MICU1 inhibiting the uniporter.","subject":{"id":"c2396324-d42c-57ce-94be-43ac8930329e","slug":"micu1","display_name":"Mitochondrial calcium uptake protein 1 / MICU1","entity_type_key":"protein"},"object":{"id":"200eff80-420c-52f8-a4c5-4f5188b7b78b","slug":"mitochondrial-calcium-uniporter-complex","display_name":"Mitochondrial calcium uniporter complex","entity_type_key":"protein_complex"},"evidence_count":1,"mechanism_event":{"id":"5784f3c6-42da-5cdf-96d8-fe5c09b28a1a","stable_key":"434e1e27-eb90-583a-956b-62472726ffba:ca-micu1-occlusion-evidence-event","event_type":"mechanistic_evidence","label":"A later study directly observes MICU1 inhibiting the uniporter.","description":"Purified MICU1 suppresses MCU-complex currents in patch-clamp experiments, and disruption of its MCU-interacting K126 residue abolishes this suppression.","status":"provisional","compartment":{"slug":"mitochondrial-intermembrane-space","display_name":"Mitochondrial intermembrane space"},"participants":[{"entity":{"id":"c2396324-d42c-57ce-94be-43ac8930329e","slug":"micu1","display_name":"Mitochondrial calcium uptake protein 1 / MICU1","entity_type_key":"protein"},"role":"channel_inhibitor","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"200eff80-420c-52f8-a4c5-4f5188b7b78b","slug":"mitochondrial-calcium-uniporter-complex","display_name":"Mitochondrial calcium uniporter complex","entity_type_key":"protein_complex"},"role":"regulated_channel_complex","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"e359bc15-e675-5d83-b0fe-1d70814e130b","slug":"calcium-ion","display_name":"Calcium ion","entity_type_key":"ion"},"role":"transported_substrate","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"3e8234e8-3e7d-59e4-b823-26154b7aac96","slug":"smdt1","display_name":"Essential MCU regulator / EMRE / SMDT1","entity_type_key":"protein"},"role":"auxiliary_subunit","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"05f933b8-964c-5007-9422-579ac96ba1d1","slug":"mitochondrial-intermembrane-space","display_name":"Mitochondrial intermembrane space","entity_type_key":"organelle"},"role":"experimental_location","stoichiometry":null,"state_label":"","sequence_order":4,"notes":"Study location; presence here is not a separate transport or causal claim."},{"entity":{"id":"4896b3f4-07bf-56d2-a369-c421f8b37ace","slug":"inner-mitochondrial-membrane","display_name":"Inner mitochondrial membrane","entity_type_key":"organelle"},"role":"experimental_location","stoichiometry":null,"state_label":"","sequence_order":5,"notes":"Study location; presence here is not a separate transport or causal claim."}]},"contexts":[{"dimension":"compartment_description","value_text":"Intermembrane-space face of inner mitochondrial membrane","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Purified MICU1 addition, mitoplast patch clamp and intact mitochondrial ion-flux assays","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Supports pore occlusion in these assays; competing potentiation evidence remains linked rather than discarded.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Calcium research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"calcium","display_name":"Calcium","entity_type_key":"nutrient_element"}},{"dimension":"organism","value_text":"Mammalia","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"A later study directly observes MICU1 inhibiting the uniporter.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[ca-tsai2023] Evidence supporting the MICU1 occlusion mechanism and against the potentiation model in the mitochondrial calcium uniporter complex (2023). https://pubmed.ncbi.nlm.nih.gov/37036971/ DOI: 10.1073/pnas.2217665120","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"research_relationship_category","value_text":"mechanistic_evidence","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Reconstituted protein and mitochondrial preparations","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"e1efc967-9996-5c65-9f7b-6a93f4180a3a","evidence_kind":"source_excerpt","locator":"Lines 757-768","start_line":757,"end_line":768,"excerpt":"### ca-micu1-occlusion-evidence\nPurified MICU1 suppresses MCU-complex currents in patch-clamp experiments, and disruption of its MCU-interacting K126 residue abolishes this suppression.\nCondition category: normal\nnutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: A later study directly observes MICU1 inhibiting the uniporter.\norganism: Mammalia\ntissue_or_cell_type: Reconstituted protein and mitochondrial preparations\nexperimental_model: Purified MICU1 addition, mitoplast patch clamp and intact mitochondrial ion-flux assays\nlimitations: Supports pore occlusion in these assays; competing potentiation evidence remains linked rather than discarded.\nresearch_relationship_category: mechanistic_evidence\ncompartment_description: Intermembrane-space face of inner mitochondrial membrane\n[ca-tsai2023] Evidence supporting the MICU1 occlusion mechanism and against the potentiation model in the mitochondrial calcium uniporter complex (2023). https://pubmed.ncbi.nlm.nih.gov/37036971/ DOI: 10.1073/pnas.2217665120","model_system":"Purified MICU1 addition, mitoplast patch clamp and intact mitochondrial ion-flux assays","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [ca-tsai2023] Evidence supporting the MICU1 occlusion mechanism and against the potentiation model in the mitochondrial calcium uniporter complex (2023). https://pubmed.ncbi.nlm.nih.gov/37036971/ DOI: 10.1073/pnas.2217665120","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"3c083fa0-59c6-50e9-af42-678d0e3c1006","stable_key":"import-434e1e27-eb90-583a-956b-62472726ffba","title":"Calcium: mechanism-first literature curation (2026-09-17)","document_type":"imported_text","citation_label":"AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text.","file_path":"","sha256":"965c934d6b147f2b62f8d45ce6d7a87681a600bfe5c46a585b4704889afd3fc1","revision_id":"543ec48b-4f70-5197-9d76-f5a3c443664c","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[{"id":"ce2b5820-97c9-5c81-b1d9-d8228bdeb851","title":"MICU1 pore occlusion versus allosteric potentiation","kind":"contradiction","status":"open","why":"Garg 2021 interprets currents as MICU-dependent potentiation without occlusion; Tsai 2023 directly observes MICU1 inhibition and identifies preparation/subunit-composition effects.","resolution":"Curation interpretation: Keep both source-specific claims. Later inhibition experiments support occlusion and challenge the prior interpretation, but avoid presenting a single assay-derived model as universal across tissues.","created_at":"2026-09-17 08:08:54","record_type":"conflict","display_label":"Recorded conflict","record_url":"/conflicts/ce2b5820-97c9-5c81-b1d9-d8228bdeb851","sides":[{"conflict_id":"ce2b5820-97c9-5c81-b1d9-d8228bdeb851","ordinal":0,"label":"One electrophysiological study proposes that MICU proteins increase channel opening during calcium signals.","revision_id":"543ec48b-4f70-5197-9d76-f5a3c443664c","start_line":745,"end_line":755,"quote":"### ca-micu-potentiation-model\nGarg and colleagues interpret mitochondrial currents as MICU-dependent enhancement of uniporter opening at elevated external calcium, without pore occlusion.\nCondition category: normal\nnutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: One electrophysiological study proposes that MICU proteins increase channel opening during calcium signals.\norganism: Mammalia\ntissue_or_cell_type: Isolated mitochondria and mitoplasts\nexperimental_model: Isolated mammalian mitochondria and mitoplast macroscopic/single-channel patch clamp\nlimitations: Contested interpretation; mitoplast preparation and subunit abundance are challenged by Tsai 2023. Not a settled universal edge.\ncompartment_description: Inner mitochondrial membrane\n[ca-garg2021] The mechanism of MICU-dependent gating of the mitochondrial Ca2+ uniporter (2021). https://pubmed.ncbi.nlm.nih.gov/34463251/ DOI: 10.7554/eLife.69312","source_key":"import-434e1e27-eb90-583a-956b-62472726ffba","source_title":"Calcium: mechanism-first literature curation (2026-09-17)","claim_ids":["7de32da1-db07-52fa-9ef8-b6e175c3ddaf"]},{"conflict_id":"ce2b5820-97c9-5c81-b1d9-d8228bdeb851","ordinal":1,"label":"A later study directly observes MICU1 inhibiting the uniporter.","revision_id":"543ec48b-4f70-5197-9d76-f5a3c443664c","start_line":757,"end_line":768,"quote":"### ca-micu1-occlusion-evidence\nPurified MICU1 suppresses MCU-complex currents in patch-clamp experiments, and disruption of its MCU-interacting K126 residue abolishes this suppression.\nCondition category: normal\nnutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: A later study directly observes MICU1 inhibiting the uniporter.\norganism: Mammalia\ntissue_or_cell_type: Reconstituted protein and mitochondrial preparations\nexperimental_model: Purified MICU1 addition, mitoplast patch clamp and intact mitochondrial ion-flux assays\nlimitations: Supports pore occlusion in these assays; competing potentiation evidence remains linked rather than discarded.\nresearch_relationship_category: mechanistic_evidence\ncompartment_description: Intermembrane-space face of inner mitochondrial membrane\n[ca-tsai2023] Evidence supporting the MICU1 occlusion mechanism and against the potentiation model in the mitochondrial calcium uniporter complex (2023). https://pubmed.ncbi.nlm.nih.gov/37036971/ DOI: 10.1073/pnas.2217665120","source_key":"import-434e1e27-eb90-583a-956b-62472726ffba","source_title":"Calcium: mechanism-first literature curation (2026-09-17)","claim_ids":["d09a4c41-f1c5-5ac4-908d-14f8656c8419"]},{"conflict_id":"ce2b5820-97c9-5c81-b1d9-d8228bdeb851","ordinal":2,"label":"MICU1 helps prevent unnecessary calcium accumulation in resting mitochondria.","revision_id":"543ec48b-4f70-5197-9d76-f5a3c443664c","start_line":706,"end_line":717,"quote":"### ca-micu1-basal-uptake-restraint\nMICU1 limits MCU-dependent calcium uptake at low external calcium in the examined cell preparations.\nCondition category: normal\nnutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: MICU1 helps prevent unnecessary calcium accumulation in resting mitochondria.\norganism: Homo sapiens\ntissue_or_cell_type: HeLa, HEK293 and endothelial cells\nexperimental_model: HeLa, HEK293 and human endothelial-cell knockdown; calcium-flux and stress assays\nlimitations: Threshold and molecular explanation are assay-dependent; see the separate MICU1 gating conflict.\nresearch_relationship_category: regulation\ncompartment_description: Mitochondrial uniporter regulatory machinery\n[ca-mallilankaraman2012] MICU1 is an essential gatekeeper for MCU-mediated mitochondrial Ca2+ uptake that regulates cell survival (2012). https://pubmed.ncbi.nlm.nih.gov/23101630/ DOI: 10.1016/j.cell.2012.10.011","source_key":"import-434e1e27-eb90-583a-956b-62472726ffba","source_title":"Calcium: mechanism-first literature curation (2026-09-17)","claim_ids":["9a3052f7-45a2-5206-846f-c611b200084b"]}]}],"corrections":[],"research":null}