{"id":"364e38a0-94d1-5e79-b7cb-21c53845100c","stable_key":"88eb7407-f147-558b-889b-0c89c4e0aa4a:spermidine-liver-dohh-failure","predicate":"knockdown_prevents","statement":"Dohh siRNA prevented spermidine rescue of mitochondrial protein expression and respiration under fatty-acid stress.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"e7ec2d34-a9b4-53c8-b160-cdbf4abf5189","mechanism_event_label":"More spermidine could not bypass the missing enzyme.","subject":{"id":"58abfecd-ab4c-5401-87da-41ea8ebfed6d","slug":"mouse-dohh","display_name":"Mouse deoxyhypusine hydroxylase / Dohh","entity_type_key":"protein"},"object":{"id":"3268b0bf-3f4c-5e63-8cb6-b3b68ac69098","slug":"mouse-aml12-mitochondrial-respiration","display_name":"Mouse AML12 mitochondrial respiration","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"e7ec2d34-a9b4-53c8-b160-cdbf4abf5189","stable_key":"88eb7407-f147-558b-889b-0c89c4e0aa4a:spermidine-liver-dohh-failure-event","event_type":"observed_relationship","label":"More spermidine could not bypass the missing enzyme.","description":"Dohh siRNA prevented spermidine rescue of mitochondrial protein expression and respiration under fatty-acid stress.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"58abfecd-ab4c-5401-87da-41ea8ebfed6d","slug":"mouse-dohh","display_name":"Mouse deoxyhypusine hydroxylase / Dohh","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"3268b0bf-3f4c-5e63-8cb6-b3b68ac69098","slug":"mouse-aml12-mitochondrial-respiration","display_name":"Mouse AML12 mitochondrial respiration","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"7014993c-468f-5c6b-ab04-80c87f9dfd9f","slug":"spermidine","display_name":"Spermidine","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"evidence_access","value_text":"Primary full text","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Mouse AML12 cells; genetic knockdown and rescue design.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Does not imply that all low DOHH activity is caused by iron deficiency.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Spermidine collection; molecular form, preparation, species, exposure and manipulation remain explicit.","comparator":null,"unit":null,"notes":"","entity":{"slug":"spermidine","display_name":"Spermidine","entity_type_key":"small_molecule"}},{"dimension":"plain_language","value_text":"More spermidine could not bypass the missing enzyme.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Spermidine-mediated hypusination of translation factor EIF5A improves mitochondrial fatty acid oxidation and prevents non-alcoholic steatohepatitis progression. · 2022 · https://pubmed.ncbi.nlm.nih.gov/36057633/ · DOI 10.1038/s41467-022-32788-x","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":"ac91b9d8-3e63-52de-994b-0f07545f02a9","evidence_kind":"source_excerpt","locator":"Lines 310-316","start_line":310,"end_line":316,"excerpt":"## spermidine-liver-dohh-failure\nMore spermidine could not bypass the missing enzyme.\nDohh siRNA prevented spermidine rescue of mitochondrial protein expression and respiration under fatty-acid stress.\nModel: Mouse AML12 cells; genetic knockdown and rescue design.\nLimitations: Does not imply that all low DOHH activity is caused by iron deficiency.\nEvidence access: Primary full text\nSpermidine-mediated hypusination of translation factor EIF5A improves mitochondrial fatty acid oxidation and prevents non-alcoholic steatohepatitis progression. · 2022 · https://pubmed.ncbi.nlm.nih.gov/36057633/ · DOI 10.1038/s41467-022-32788-x","model_system":"Mouse AML12 cells; genetic knockdown and rescue design.","directness":"reported_statement","verification_status":"source_derived_draft","notes":"Original curation paraphrase; evidence access and experimental limitations specified.","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"4348f3f8-0180-58a3-b61c-55d03bb322d2","stable_key":"import-88eb7407-f147-558b-889b-0c89c4e0aa4a","title":"Spermidine: biosynthesis, hypusination, transport and cross-nutrient mechanisms (2026-09-19)","document_type":"imported_text","citation_label":"AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text.","file_path":"","sha256":"8eec8784bc2bd0384cfd53c6603c4ced8e53c227d9ab29ed85594c43e34c68ef","revision_id":"7c421a18-4526-59f6-b84e-4be533bc35ac","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}