{"id":"97620727-99dc-5cb1-a80e-7d219b19cece","stable_key":"434e1e27-eb90-583a-956b-62472726ffba:ca-overload-permeability-transition","predicate":"promotes","statement":"Calcium-overload conditions induce cyclophilin-D-sensitive mitochondrial permeability transition and swelling in the tested mouse preparations.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"32228d16-bc42-5044-ac0c-8e48f5e4e08b","mechanism_event_label":"Excess mitochondrial calcium can trigger membrane permeability failure.","subject":{"id":"e359bc15-e675-5d83-b0fe-1d70814e130b","slug":"calcium-ion","display_name":"Calcium ion","entity_type_key":"ion"},"object":{"id":"bcb87e8d-5a43-5c26-926a-ffc24ae61493","slug":"mitochondrial-permeability-transition","display_name":"Mitochondrial permeability transition","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"32228d16-bc42-5044-ac0c-8e48f5e4e08b","stable_key":"434e1e27-eb90-583a-956b-62472726ffba:ca-overload-permeability-transition-event","event_type":"exposure_response","label":"Excess mitochondrial calcium can trigger membrane permeability failure.","description":"Calcium-overload conditions induce cyclophilin-D-sensitive mitochondrial permeability transition and swelling in the tested mouse preparations.","status":"provisional","compartment":{"slug":"inner-mitochondrial-membrane","display_name":"Inner mitochondrial membrane"},"participants":[{"entity":{"id":"e359bc15-e675-5d83-b0fe-1d70814e130b","slug":"calcium-ion","display_name":"Calcium ion","entity_type_key":"ion"},"role":"overload_trigger","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"bfcc9d68-c8d5-5e96-bd88-495b37c79487","slug":"ppif","display_name":"Mitochondrial cyclophilin D / PPIF","entity_type_key":"protein"},"role":"permissive_regulator","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"bcb87e8d-5a43-5c26-926a-ffc24ae61493","slug":"mitochondrial-permeability-transition","display_name":"Mitochondrial permeability transition","entity_type_key":"cellular_process"},"role":"response","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"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":3,"notes":"Study location; presence here is not a separate transport or causal claim."},{"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":"compartment_description","value_text":"Inner mitochondrial membrane and matrix","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Ppif-null and cyclophilin-D-overexpressing mice; isolated mitochondria, hepatocytes and fibroblasts","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Experimental overload; not all apoptosis uses this pathway and the study does not settle the molecular identity of the pore.","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":"Mus musculus","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Excess mitochondrial calcium can trigger membrane permeability failure.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[ca-baines2005] Loss of cyclophilin D reveals a critical role for mitochondrial permeability transition in cell death (2005). https://pubmed.ncbi.nlm.nih.gov/15800627/ DOI: 10.1038/nature03434","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"research_relationship_category","value_text":"exposure_response","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Isolated liver, heart and brain mitochondria","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"908ee722-199a-5d0e-ad61-b78fddeed9aa","evidence_kind":"source_excerpt","locator":"Lines 836-847","start_line":836,"end_line":847,"excerpt":"### ca-overload-permeability-transition\nCalcium-overload conditions induce cyclophilin-D-sensitive mitochondrial permeability transition and swelling in the tested mouse preparations.\nCondition category: normal\nnutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Excess mitochondrial calcium can trigger membrane permeability failure.\norganism: Mus musculus\ntissue_or_cell_type: Isolated liver, heart and brain mitochondria\nexperimental_model: Ppif-null and cyclophilin-D-overexpressing mice; isolated mitochondria, hepatocytes and fibroblasts\nlimitations: Experimental overload; not all apoptosis uses this pathway and the study does not settle the molecular identity of the pore.\nresearch_relationship_category: exposure_response\ncompartment_description: Inner mitochondrial membrane and matrix\n[ca-baines2005] Loss of cyclophilin D reveals a critical role for mitochondrial permeability transition in cell death (2005). https://pubmed.ncbi.nlm.nih.gov/15800627/ DOI: 10.1038/nature03434","model_system":"Ppif-null and cyclophilin-D-overexpressing mice; isolated mitochondria, hepatocytes and fibroblasts","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [ca-baines2005] Loss of cyclophilin D reveals a critical role for mitochondrial permeability transition in cell death (2005). https://pubmed.ncbi.nlm.nih.gov/15800627/ DOI: 10.1038/nature03434","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":"e682d428-ce0e-57d0-a13d-e63383fa9244","title":"Calcium-overload permeability transition is not a universal apoptosis pathway","kind":"qualification","status":"open","why":"Baines 2005 reports resistance to calcium-overload/oxidative injury after Ppif loss but retained susceptibility to several other death stimuli.","resolution":"Curation interpretation: Represent the calcium-overload response with its exposure and cellular model; do not infer that all apoptosis requires calcium overload or cyclophilin D.","created_at":"2026-09-17 08:08:54","record_type":"conflict","display_label":"Recorded conflict","record_url":"/conflicts/e682d428-ce0e-57d0-a13d-e63383fa9244","sides":[{"conflict_id":"e682d428-ce0e-57d0-a13d-e63383fa9244","ordinal":0,"label":"Excess mitochondrial calcium can trigger membrane permeability failure.","revision_id":"543ec48b-4f70-5197-9d76-f5a3c443664c","start_line":836,"end_line":847,"quote":"### ca-overload-permeability-transition\nCalcium-overload conditions induce cyclophilin-D-sensitive mitochondrial permeability transition and swelling in the tested mouse preparations.\nCondition category: normal\nnutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Excess mitochondrial calcium can trigger membrane permeability failure.\norganism: Mus musculus\ntissue_or_cell_type: Isolated liver, heart and brain mitochondria\nexperimental_model: Ppif-null and cyclophilin-D-overexpressing mice; isolated mitochondria, hepatocytes and fibroblasts\nlimitations: Experimental overload; not all apoptosis uses this pathway and the study does not settle the molecular identity of the pore.\nresearch_relationship_category: exposure_response\ncompartment_description: Inner mitochondrial membrane and matrix\n[ca-baines2005] Loss of cyclophilin D reveals a critical role for mitochondrial permeability transition in cell death (2005). https://pubmed.ncbi.nlm.nih.gov/15800627/ DOI: 10.1038/nature03434","source_key":"import-434e1e27-eb90-583a-956b-62472726ffba","source_title":"Calcium: mechanism-first literature curation (2026-09-17)","claim_ids":["97620727-99dc-5cb1-a80e-7d219b19cece"]},{"conflict_id":"e682d428-ce0e-57d0-a13d-e63383fa9244","ordinal":1,"label":"Removing cyclophilin D protects these cells against calcium-overload injury.","revision_id":"543ec48b-4f70-5197-9d76-f5a3c443664c","start_line":849,"end_line":860,"quote":"### ca-ppif-loss-calcium-death-resistance\nPpif-null hepatocytes and fibroblasts resist calcium-overload-induced death relative to wild type.\nCondition category: machinery_impairment\nnutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Removing cyclophilin D protects these cells against calcium-overload injury.\norganism: Mus musculus\ntissue_or_cell_type: Primary hepatocytes and fibroblasts\nexperimental_model: Ppif-null and cyclophilin-D-overexpressing mice; isolated mitochondria, hepatocytes and fibroblasts\nlimitations: Protection does not extend to all classical apoptotic stimuli; calcium nutrition was not manipulated.\nresearch_relationship_category: loss_of_function\ncompartment_description: Mitochondrial permeability-transition pathway\n[ca-baines2005] Loss of cyclophilin D reveals a critical role for mitochondrial permeability transition in cell death (2005). https://pubmed.ncbi.nlm.nih.gov/15800627/ DOI: 10.1038/nature03434","source_key":"import-434e1e27-eb90-583a-956b-62472726ffba","source_title":"Calcium: mechanism-first literature curation (2026-09-17)","claim_ids":["99321590-24df-5cbc-84d7-1fff38be2876"]}]}],"corrections":[],"research":null}