{"id":"26cd0fcc-5565-5ff7-9a6c-4aec48cad0a9","stable_key":"fe6af7fc-7372-5c4f-9c2f-2bbf56695397:phosphorus-pi-mito-peroxide","predicate":"increases","statement":"The study linked phosphate entry into mitochondria to increased hydrogen-peroxide production in the FGFR1 activation pathway.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"19fde1f7-549c-52cf-80bb-d3f01eddefe0","mechanism_event_label":"Mitochondrial phosphate handling fed a redox signal in these tumor models.","subject":{"id":"ee63fe8e-92f3-552f-8049-a5f1fa1e1523","slug":"phosphate-ion","display_name":"Inorganic phosphate (Pi; protonation depends on pH)","entity_type_key":"ion"},"object":{"id":"c0189c73-22c6-5714-a82b-3c68e1a05040","slug":"osteosarcoma-mitochondrial-h2o2","display_name":"Mitochondrial hydrogen-peroxide production in the 2026 osteosarcoma study","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"19fde1f7-549c-52cf-80bb-d3f01eddefe0","stable_key":"fe6af7fc-7372-5c4f-9c2f-2bbf56695397:phosphorus-pi-mito-peroxide-event","event_type":"biochemical_relationship","label":"Mitochondrial phosphate handling fed a redox signal in these tumor models.","description":"The study linked phosphate entry into mitochondria to increased hydrogen-peroxide production in the FGFR1 activation pathway.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"da9d64bc-69d4-5d97-90a4-8f0ed03e0ac8","slug":"hydrogen-peroxide","display_name":"Hydrogen peroxide","entity_type_key":"small_molecule"},"role":"signal_species","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"ee63fe8e-92f3-552f-8049-a5f1fa1e1523","slug":"phosphate-ion","display_name":"Inorganic phosphate (Pi; protonation depends on pH)","entity_type_key":"ion"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"c0189c73-22c6-5714-a82b-3c68e1a05040","slug":"osteosarcoma-mitochondrial-h2o2","display_name":"Mitochondrial hydrogen-peroxide production in the 2026 osteosarcoma study","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/phosphorus-research/42247296.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"a8d4221d8a5c56a5937ab8262e3ece5ed87692cb876ddcc0a08e7f68b66a9b76\", \"start_char\": 0, \"end_char\": 1041, \"text_sha256\": \"a8d4221d8a5c56a5937ab8262e3ece5ed87692cb876ddcc0a08e7f68b66a9b76\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Osteosarcoma-cell signaling with in-vivo tumor experiments","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Elevated phosphate challenges and receptor activation experiments","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"New 2026 mechanism in tumor models; blood-Pi/tumor-growth association is not proof that dietary phosphorus causes human cancer. No specific transporter or oxidized residue number is invented from the abstract.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Phosphorus research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"phosphorus","display_name":"Phosphorus","entity_type_key":"nutrient_element"}},{"dimension":"organism","value_text":"Osteosarcoma cellular and animal systems; precise species not fully resolved from abstract","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Mitochondrial phosphate handling fed a redox signal in these tumor models.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[phosphorus-p42247296] Unconventional activation of the proto-oncogene FGFR1 by extracellular phosphate via H2O2-mediated kinase oxidation. (2026). https://pubmed.ncbi.nlm.nih.gov/42247296/ DOI: 10.1016/j.celrep.2026.117504","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Plasma-membrane/mitochondrial phosphate handling and FGFR1 signaling","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"067a7730-bfb3-53df-862b-cf0ea6468ab3","evidence_kind":"source_excerpt","locator":"Lines 867-878","start_line":867,"end_line":878,"excerpt":"### phosphorus-pi-mito-peroxide\nThe study linked phosphate entry into mitochondria to increased hydrogen-peroxide production in the FGFR1 activation pathway.\nCondition category: normal\nnutrient_topic: Phosphorus research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Mitochondrial phosphate handling fed a redox signal in these tumor models.\norganism: Osteosarcoma cellular and animal systems; precise species not fully resolved from abstract\ntissue_or_cell_type: Plasma-membrane/mitochondrial phosphate handling and FGFR1 signaling\nexperimental_model: Osteosarcoma-cell signaling with in-vivo tumor experiments\nlimitations: New 2026 mechanism in tumor models; blood-Pi/tumor-growth association is not proof that dietary phosphorus causes human cancer. No specific transporter or oxidized residue number is invented from the abstract.\nexposure: Elevated phosphate challenges and receptor activation experiments\nevidence_span: {\"source_cache\": \"artifacts/phosphorus-research/42247296.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"a8d4221d8a5c56a5937ab8262e3ece5ed87692cb876ddcc0a08e7f68b66a9b76\", \"start_char\": 0, \"end_char\": 1041, \"text_sha256\": \"a8d4221d8a5c56a5937ab8262e3ece5ed87692cb876ddcc0a08e7f68b66a9b76\"}\n[phosphorus-p42247296] Unconventional activation of the proto-oncogene FGFR1 by extracellular phosphate via H2O2-mediated kinase oxidation. 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