{"id":"414c312d-359c-56af-b778-e245eb7f2c94","stable_key":"8b3cf083-ea9c-54f5-b42b-bf1fef5b2978:metformin-complex-i-respiration","predicate":"reduces","statement":"Cellular respiration fell with metformin, and cells relied exclusively on glycolysis for survival in its presence.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"e4094dfd-c61b-5c52-931a-f904d7cb6b90","mechanism_event_label":"With the chain slowed, the cell falls back on the oxygen-free route.","subject":{"id":"519971b1-5aef-5ad7-8022-840144855cd0","slug":"metformin","display_name":"Metformin","entity_type_key":"drug"},"object":{"id":"8517d687-6fac-589a-81a0-ef681cf2307f","slug":"cellular-respiration","display_name":"Cellular mitochondrial respiration","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"e4094dfd-c61b-5c52-931a-f904d7cb6b90","stable_key":"8b3cf083-ea9c-54f5-b42b-bf1fef5b2978:metformin-complex-i-respiration-event","event_type":"biochemical_relationship","label":"With the chain slowed, the cell falls back on the oxygen-free route.","description":"Cellular respiration fell with metformin, and cells relied exclusively on glycolysis for survival in its presence.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"519971b1-5aef-5ad7-8022-840144855cd0","slug":"metformin","display_name":"Metformin","entity_type_key":"drug"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"8517d687-6fac-589a-81a0-ef681cf2307f","slug":"cellular-respiration","display_name":"Cellular mitochondrial respiration","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/metformin-research/24843020.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"21403805272b0d702f0f60887d805b1e52b4ce87a9335fcde1d34cefda8b16ae\", \"start_char\": 0, \"end_char\": 1142, \"text_sha256\": \"21403805272b0d702f0f60887d805b1e52b4ce87a9335fcde1d34cefda8b16ae\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Human cancer cells and mouse xenografts with the metformin-resistant yeast NDI1 as a genetic rescue","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Metformin in the presence and absence of glucose; NDI1 overexpression","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Cancer-cell concentrations are far above therapeutic plasma levels. The NDI1 rescue is strong evidence that the effects run through complex I in this model, not evidence of an antitumour indication.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Metformin research collection; topical membership is not evidence of a direct clinical effect, and pharmacological exposure is not dietary intake.","comparator":null,"unit":null,"notes":"","entity":{"slug":"metformin","display_name":"Metformin","entity_type_key":"drug"}},{"dimension":"organism","value_text":"Human cells; mouse in vivo","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"With the chain slowed, the cell falls back on the oxygen-free route.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[metformin-p24843020] Metformin inhibits mitochondrial complex I of cancer cells to reduce tumorigenesis. 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The NDI1 rescue is strong evidence that the effects run through complex I in this model, not evidence of an antitumour indication.\nexposure: Metformin in the presence and absence of glucose; NDI1 overexpression\nevidence_span: {\"source_cache\": \"artifacts/metformin-research/24843020.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"21403805272b0d702f0f60887d805b1e52b4ce87a9335fcde1d34cefda8b16ae\", \"start_char\": 0, \"end_char\": 1142, \"text_sha256\": \"21403805272b0d702f0f60887d805b1e52b4ce87a9335fcde1d34cefda8b16ae\"}\n[metformin-p24843020] Metformin inhibits mitochondrial complex I of cancer cells to reduce tumorigenesis. 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