{"id":"8335fda9-b768-5313-86c9-8e277a32d85c","stable_key":"434e1e27-eb90-583a-956b-62472726ffba:ca-micu1-loss-overload","predicate":"limits","statement":"MICU1 knockdown elevates basal matrix calcium through MCU-dependent uptake in the tested cells.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"1650e30d-6dd6-56d5-8923-d9515082d41d","mechanism_event_label":"Loss of MICU1 can let mitochondria accumulate too much calcium at rest.","subject":{"id":"c2396324-d42c-57ce-94be-43ac8930329e","slug":"micu1","display_name":"Mitochondrial calcium uptake protein 1 / MICU1","entity_type_key":"protein"},"object":{"id":"0c2b6491-25e5-5f0f-8a04-82ffe29a8537","slug":"mitochondrial-calcium-overload","display_name":"Mitochondrial calcium overload","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"1650e30d-6dd6-56d5-8923-d9515082d41d","stable_key":"434e1e27-eb90-583a-956b-62472726ffba:ca-micu1-loss-overload-event","event_type":"loss_of_function","label":"Loss of MICU1 can let mitochondria accumulate too much calcium at rest.","description":"MICU1 knockdown elevates basal matrix calcium through MCU-dependent uptake in the tested cells.","status":"provisional","compartment":{"slug":"mitochondrial-matrix","display_name":"Mitochondrial matrix"},"participants":[{"entity":{"id":"c2396324-d42c-57ce-94be-43ac8930329e","slug":"micu1","display_name":"Mitochondrial calcium uptake protein 1 / MICU1","entity_type_key":"protein"},"role":"impaired_regulator","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"8327f938-e484-5212-9580-7446b5c68ad8","slug":"mcu","display_name":"Mitochondrial calcium uniporter pore protein / MCU","entity_type_key":"protein"},"role":"channel","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":"accumulating_ion","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"0c2b6491-25e5-5f0f-8a04-82ffe29a8537","slug":"mitochondrial-calcium-overload","display_name":"Mitochondrial calcium overload","entity_type_key":"cellular_process"},"role":"affected_process","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"1f2cf4a9-0168-5691-8b00-1676e5a477e1","slug":"mitochondrial-matrix","display_name":"Mitochondrial matrix","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."}]},"contexts":[{"dimension":"availability_state","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"compartment_description","value_text":"Mitochondrial matrix","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"HeLa, HEK293 and human endothelial-cell knockdown; calcium-flux and stress assays","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Cell-specific knockdown response; does not imply high dietary calcium or all MICU1 variants behave identically.","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":"Homo sapiens","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Loss of MICU1 can let mitochondria accumulate too much calcium at rest.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[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","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"research_relationship_category","value_text":"loss_of_function","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"HeLa and endothelial cells","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"trigger_kind","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null}],"evidence":[{"id":"498f4bc1-23fe-5f4d-824b-ec54c962eb1d","evidence_kind":"source_excerpt","locator":"Lines 719-730","start_line":719,"end_line":730,"excerpt":"### ca-micu1-loss-overload\nMICU1 knockdown elevates basal matrix calcium through MCU-dependent uptake in the tested cells.\nCondition category: machinery_impairment\nnutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Loss of MICU1 can let mitochondria accumulate too much calcium at rest.\norganism: Homo sapiens\ntissue_or_cell_type: HeLa and endothelial cells\nexperimental_model: HeLa, HEK293 and human endothelial-cell knockdown; calcium-flux and stress assays\nlimitations: Cell-specific knockdown response; does not imply high dietary calcium or all MICU1 variants behave identically.\nresearch_relationship_category: loss_of_function\ncompartment_description: Mitochondrial matrix\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","model_system":"HeLa, HEK293 and human endothelial-cell knockdown; calcium-flux and stress assays","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [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","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":[],"corrections":[],"research":null}