A PPIX-binding probe facilitates discovery of PPIX-induced cell death modulation by peroxiredoxin.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:37355765", "kind": "science-record", "revision": 3, "content_hash": "sha256:89490bf9736de651b0f1c7d1451523d37facdb20f4af7fbeb1cddd69d3e23a6c", "created_at": "2026-11-01T19:02:05Z", "updated_at": "2026-11-01T22:09:44Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "A PPIX-binding probe facilitates discovery of PPIX-induced cell death modulation by peroxiredoxin.", "doi": "10.1038/s42003-023-05024-5", "pmid": "37355765", "authors": ["John Lynch", "Yao Wang", "Yuxin Li", "Kanisha Kavdia", "Yu Fukuda", "Sabina Ranjit", "Camenzind G Robinson", "Christy R Grace", "Youlin Xia", "Junmin Peng", "John D Schuetz"], "journal": "Communications biology", "year": 2023, "abstract": "While heme synthesis requires the formation of a potentially lethal intermediate, protoporphyrin IX (PPIX), surprisingly little is known about the mechanism of its toxicity, aside from its phototoxicity. The cellular protein interactions of PPIX might provide insight into modulators of PPIX-induced cell death. Here we report the development of PPB, a biotin-conjugated, PPIX-probe that captures proteins capable of interacting with PPIX. Quantitative proteomics in a diverse panel of mammalian cell lines reveal a high degree of concordance for PPB-interacting proteins identified for each cell line. Most differences are quantitative, despite marked differences in PPIX formation and sensitivity. Pathway and quantitative difference analysis indicate that iron and heme metabolism proteins are prominent among PPB-bound proteins in fibroblasts, which undergo PPIX-mediated death determined to occur through ferroptosis. PPB proteomic data (available at PRIDE ProteomeXchange # PXD042631) reveal that redox proteins from PRDX family of glutathione peroxidases interact with PPIX. Targeted gene knockdown of the mitochondrial PRDX3, but not PRDX1 or 2, enhance PPIX-induced death in fibroblasts, an effect blocked by the radical-trapping antioxidant, ferrostatin-1. Increased PPIX formation and death was also observed in a T-lymphoblastoid ferrochelatase-deficient leukemia cell line, suggesting that PPIX elevation might serve as a potential strategy for killing certain leukemias.", "claims": [{"id": "claim-data-access", "statement": "Proteomic data will be available through the Dryad data depository via 10.5061/dryad.mkkwh712t. Numerical source data for all charts and graphs is available in Supplementary Data Table 1. Original images for figures may be found, as Supplementary Figs. 12–25, in the Supplementary Information file. Any other data will be provided upon request of the corresponding author.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37355765", "locator": "sections[45] \"Data availability\" paragraph 2", "quote": "Proteomic data will be available through the Dryad data depository via 10.5061/dryad.mkkwh712t. Numerical source data for all charts and graphs is available in Supplementary Data Table 1. Original images for figures may be found, as Supplementary Figs. 12–25, in the Supplementary Information file. Any other data will be provided upon request of the corresponding author."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Quantitative TMT proteomics identified 543 discrete PPB-interacting protein candidates.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:37355765", "locator": "sections[6] \"Identification of PPB-interacting proteins\" paragraph 2", "quote": "In total, 543 discrete specific candidates were identified as PPB-interacting proteins (FDR < 0.01 and z-score >3; Supplementary Data 1, see tab Data Candidates)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Quantitative TMT proteomics identified 543 discrete PPB-interacting protein candidates.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:37355765"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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