{"id":"c10dc4f6-59c1-51ab-99c9-17d2d5608699","stable_key":"8b3cf083-ea9c-54f5-b42b-bf1fef5b2978:metformin-complex-i-inhibition","predicate":"inhibits","statement":"Metformin inhibited mitochondrial complex I (NADH dehydrogenase) activity and cellular respiration in human cancer cells.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"a7d85902-9fe7-5dbd-9ffb-0a9e242fbfc9","mechanism_event_label":"The drug slows the first station of the mitochondrial energy chain.","subject":{"id":"519971b1-5aef-5ad7-8022-840144855cd0","slug":"metformin","display_name":"Metformin","entity_type_key":"drug"},"object":{"id":"5cd08cb7-cf10-5a19-a745-9008423a7908","slug":"cellular-complex-i-activity","display_name":"Mitochondrial complex I (NADH dehydrogenase) activity","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"a7d85902-9fe7-5dbd-9ffb-0a9e242fbfc9","stable_key":"8b3cf083-ea9c-54f5-b42b-bf1fef5b2978:metformin-complex-i-inhibition-event","event_type":"biochemical_relationship","label":"The drug slows the first station of the mitochondrial energy chain.","description":"Metformin inhibited mitochondrial complex I (NADH dehydrogenase) activity and cellular respiration in human cancer cells.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"f67ac698-de2e-55f5-8975-305eaadbb751","slug":"respiratory-complex-i","display_name":"Mitochondrial respiratory complex I","entity_type_key":"protein_complex"},"role":"inhibited_complex","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"519971b1-5aef-5ad7-8022-840144855cd0","slug":"metformin","display_name":"Metformin","entity_type_key":"drug"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"5cd08cb7-cf10-5a19-a745-9008423a7908","slug":"cellular-complex-i-activity","display_name":"Mitochondrial complex I (NADH dehydrogenase) activity","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":2,"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":"The drug slows the first station of the mitochondrial energy chain.","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. (2014). https://pubmed.ncbi.nlm.nih.gov/24843020/ DOI: 10.7554/elife.02242","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Cancer cells and tumours","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"5ef74c0d-ebc3-5483-bb92-22cf6cc3887b","evidence_kind":"source_excerpt","locator":"Lines 385-396","start_line":385,"end_line":396,"excerpt":"### metformin-complex-i-inhibition\nMetformin inhibited mitochondrial complex I (NADH dehydrogenase) activity and cellular respiration in human cancer cells.\nCondition category: normal\nnutrient_topic: Metformin research collection; topical membership is not evidence of a direct clinical effect, and pharmacological exposure is not dietary intake.\nplain_language: The drug slows the first station of the mitochondrial energy chain.\norganism: Human cells; mouse in vivo\ntissue_or_cell_type: Cancer cells and tumours\nexperimental_model: Human cancer cells and mouse xenografts with the metformin-resistant yeast NDI1 as a genetic rescue\nlimitations: 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.\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. (2014). https://pubmed.ncbi.nlm.nih.gov/24843020/ DOI: 10.7554/elife.02242","model_system":"Human cancer cells and mouse xenografts with the metformin-resistant yeast NDI1 as a genetic rescue","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [metformin-p24843020] Metformin inhibits mitochondrial complex I of cancer cells to reduce tumorigenesis. (2014). https://pubmed.ncbi.nlm.nih.gov/24843020/ DOI: 10.7554/elife.02242","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"d0474bd9-7cfd-5695-a152-12f3633a6813","stable_key":"import-8b3cf083-ea9c-54f5-b42b-bf1fef5b2978","title":"Metformin: transport, molecular targets, gut mechanisms and nutrient interactions (2026-09-19)","document_type":"imported_text","citation_label":"AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. 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