{"id":"330a96cf-6735-5f15-a9d5-5d63e4aa8c76","stable_key":"ec174d5a-4903-5745-8646-df0e9d4265e8:mitochondrial-loss-cytosolic-reversal","predicate":"redirects","statement":"MTHFD2 deletion depleted formyl-folate availability and activated cytosolic serine-derived one-carbon production.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"ba3db94e-01c1-5afc-9224-ffca794ad3ad","mechanism_event_label":"Cells can reroute carbon production after losing the mitochondrial pathway.","subject":{"id":"70f6b0c4-66a5-5593-b06b-e9bfa8bf6f7e","slug":"human-mthfd2-gene","display_name":"Human MTHFD2 gene","entity_type_key":"gene"},"object":{"id":"ae1cf62b-2ef9-52d7-bbf6-6817abb50d98","slug":"mthfd1","display_name":"Human MTHFD1","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"ba3db94e-01c1-5afc-9224-ffca794ad3ad","stable_key":"ec174d5a-4903-5745-8646-df0e9d4265e8:mitochondrial-loss-cytosolic-reversal-event","event_type":"biochemical_relationship","label":"Cells can reroute carbon production after losing the mitochondrial pathway.","description":"MTHFD2 deletion depleted formyl-folate availability and activated cytosolic serine-derived one-carbon production.","status":"provisional","compartment":{"slug":"cytosol","display_name":"Cytosol"},"participants":[{"entity":{"id":"67b21ade-d4c1-574a-a78f-b980d076ad9c","slug":"shmt1","display_name":"SHMT1","entity_type_key":"protein"},"role":"cytosolic carbon-entry enzyme","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"ec73b364-a2ea-5c4a-bcea-a54aeebf57d1","slug":"10-formyltetrahydrofolate","display_name":"10-Formyltetrahydrofolate","entity_type_key":"small_molecule"},"role":"depleted regulator","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"c882cd0b-9d83-5b07-bd1c-fe4d45657dcb","slug":"l-serine","display_name":"L-Serine","entity_type_key":"small_molecule"},"role":"carbon source","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"70f6b0c4-66a5-5593-b06b-e9bfa8bf6f7e","slug":"human-mthfd2-gene","display_name":"Human MTHFD2 gene","entity_type_key":"gene"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"ae1cf62b-2ef9-52d7-bbf6-6817abb50d98","slug":"mthfd1","display_name":"Human MTHFD1","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"experimental_model","value_text":"CRISPR and isotope tracing","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Assay conditions described in the linked primary study.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Compensation depends on nutrient availability.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"folate","display_name":"Folate (vitamin B9)","entity_type_key":"chemical_species"}},{"dimension":"organism","value_text":"Homo sapiens","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Cells can reroute carbon production after losing the mitochondrial pathway.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[ducker-2016] Reversal of Cytosolic One-Carbon Flux Compensates for Loss of the Mitochondrial Folate Pathway (2016). https://pubmed.ncbi.nlm.nih.gov/27211901/ DOI: 10.1016/j.cmet.2016.04.016","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"HEK293T cells","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":"7dcd4b0c-ea5b-597d-901c-c20329e9bdba","evidence_kind":"source_excerpt","locator":"Lines 899-909","start_line":899,"end_line":909,"excerpt":"### mitochondrial-loss-cytosolic-reversal\nMTHFD2 deletion depleted formyl-folate availability and activated cytosolic serine-derived one-carbon production.\nCondition category: machinery_impairment\nnutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Cells can reroute carbon production after losing the mitochondrial pathway.\norganism: Homo sapiens\ntissue_or_cell_type: HEK293T cells\nexperimental_model: CRISPR and isotope tracing\nlimitations: Compensation depends on nutrient availability.\nexposure: Assay conditions described in the linked primary study.\n[ducker-2016] Reversal of Cytosolic One-Carbon Flux Compensates for Loss of the Mitochondrial Folate Pathway (2016). https://pubmed.ncbi.nlm.nih.gov/27211901/ DOI: 10.1016/j.cmet.2016.04.016","model_system":"CRISPR and isotope tracing","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [ducker-2016] Reversal of Cytosolic One-Carbon Flux Compensates for Loss of the Mitochondrial Folate Pathway (2016). https://pubmed.ncbi.nlm.nih.gov/27211901/ DOI: 10.1016/j.cmet.2016.04.016","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"f4ce1a62-9582-5f7a-84f5-a23d0e1bfc68","stable_key":"import-ec174d5a-4903-5745-8646-df0e9d4265e8","title":"Folate and folic acid: mechanisms, deficiency and nutrient interactions (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":"e564d43989ece1006c95cd0748e9af6fe369074599a2eebba0a99ebff864b0dd","revision_id":"76674a33-b2a1-5e41-b71b-44399038ff7c","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}