{"id":"29ada672-f112-5c7a-b391-8131e7822a5f","stable_key":"6612c190-1948-5bcf-bbe3-a7f6c50fa3cf:l-proline-pycr1-genetic","predicate":"when_mutated_disrupts","statement":"Fibroblasts from people with PYCR1-related cutis laxa showed altered mitochondrial morphology and membrane potential and greater apoptosis during oxidative stress.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"77a175cf-437f-53ae-8ae0-6290f8c89373","mechanism_event_label":"An enzyme defect can affect connective tissue and cellular stress handling together.","subject":{"id":"6a5e6627-f4fd-5a02-b74b-371b629b076b","slug":"pycr1","display_name":"Human pyrroline-5-carboxylate reductase 1 / PYCR1","entity_type_key":"protein"},"object":{"id":"6dc3bd05-aaeb-509c-8ef6-c59b8cb134e7","slug":"human-pycr1-fibroblast-mitochondria","display_name":"Mitochondrial integrity in PYCR1-deficient human fibroblasts","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"77a175cf-437f-53ae-8ae0-6290f8c89373","stable_key":"6612c190-1948-5bcf-bbe3-a7f6c50fa3cf:l-proline-pycr1-genetic-event","event_type":"observed_relationship","label":"An enzyme defect can affect connective tissue and cellular stress handling together.","description":"Fibroblasts from people with PYCR1-related cutis laxa showed altered mitochondrial morphology and membrane potential and greater apoptosis during oxidative stress.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"6a5e6627-f4fd-5a02-b74b-371b629b076b","slug":"pycr1","display_name":"Human pyrroline-5-carboxylate reductase 1 / PYCR1","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"6dc3bd05-aaeb-509c-8ef6-c59b8cb134e7","slug":"human-pycr1-fibroblast-mitochondria","display_name":"Mitochondrial integrity in PYCR1-deficient human fibroblasts","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"70ccd53c-83ad-5251-a4f5-6370973bc40a","slug":"l-proline","display_name":"L-Proline","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 abstract","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Human genetic families and patient fibroblasts.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"The clinical disorder is not shown to be an isolated dietary proline deficiency or reliably corrected by proline supplementation. Correction record: Author correction PMID 35064218 / DOI 10.1038/s41588-022-01013-2 adds an omitted funding acknowledgment for Hulya Kayserili (TUBITAK SBAG-108S418). The notice does not report a change to the mechanism results. https://www.nature.com/articles/s41588-022-01013-2","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"L-Proline collection; species, compartment, exposure, co-substrates and manipulation remain explicit.","comparator":null,"unit":null,"notes":"","entity":{"slug":"l-proline","display_name":"L-Proline","entity_type_key":"small_molecule"}},{"dimension":"plain_language","value_text":"An enzyme defect can affect connective tissue and cellular stress handling together.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Mutations in PYCR1 cause cutis laxa with progeroid features. · 2009 · https://pubmed.ncbi.nlm.nih.gov/19648921/ · DOI 10.1038/ng.413","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":"4fe1a30a-75fe-5d12-9899-c17b5aacf046","evidence_kind":"source_excerpt","locator":"Lines 150-156","start_line":150,"end_line":156,"excerpt":"## l-proline-pycr1-genetic\nAn enzyme defect can affect connective tissue and cellular stress handling together.\nFibroblasts from people with PYCR1-related cutis laxa showed altered mitochondrial morphology and membrane potential and greater apoptosis during oxidative stress.\nModel: Human genetic families and patient fibroblasts.\nLimitations: The clinical disorder is not shown to be an isolated dietary proline deficiency or reliably corrected by proline supplementation. Correction record: Author correction PMID 35064218 / DOI 10.1038/s41588-022-01013-2 adds an omitted funding acknowledgment for Hulya Kayserili (TUBITAK SBAG-108S418). The notice does not report a change to the mechanism results. https://www.nature.com/articles/s41588-022-01013-2\nEvidence access: Primary abstract\nMutations in PYCR1 cause cutis laxa with progeroid features. · 2009 · https://pubmed.ncbi.nlm.nih.gov/19648921/ · DOI 10.1038/ng.413","model_system":"Human genetic families and patient fibroblasts.","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":"e5aa7fc5-ee52-5376-8169-416082a89fd1","stable_key":"import-6612c190-1948-5bcf-bbe3-a7f6c50fa3cf","title":"L-Proline: synthesis, collagen processing, redox metabolism 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":"7b7f1981f9c7897fbb6baa19425bdc19dede78ad4d66fa554394b8337c7366fb","revision_id":"4971a925-fa70-59f8-8030-d3029a18a62f","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}