Fig. 2: BAP1 promotes ferroptosis through mechanisms that extend beyond SLC7A11-dependent cystine metabolism.

A The Sankey diagram visualizes that the 138 genes with >1.6-fold H2Aub reduction, >1.5-fold chromatin opening, and >1.5-fold gene expression increased were enriched in the corresponding biological metabolic pathway. B Western blotting analysis of BAP1, SLC7A11, and H2Aub levels in UMRC6 cell lines. n = 3. C Relative GSH levels of indicated UMRC6 cells. D Bar graph showing cell viability in indicated cells treated with erastin (10 μM) combined with 5 μM Z-VAD-FMK (Z-VAD), 2 μM Necrostatin-1s (Nec-1s), 2 μM ferrostatin-1 (Ferr-1), or 100 μM deferoxamine (DFO). E Lipid peroxidation was assessed by flow cytometry after C11-BODIPY staining in the indicated cells treated with erastin. F Cell death was measured in SLC7A11-KO UMRC6 cells restored with BAP1 WT or C91A mutant and treated with erastin (10 μM) for 24 h. G Lipid peroxidation was assessed by flow cytometry after C11-BODIPY staining in the indicated cells treated with IKE. H Cell death was measured in SLC7A11-KO UMRC6 cells restored with BAP1 WT or C91A mutant and treated with IKE (10 μM) for 24 h. I Cell viability was measured by CCK-8 assay in SLC7A11-KO-EV, -BAP1, -C91A UMRC6 cells cultured in cystine-containing/-free medium. J Lipid peroxidation was assessed by flow cytometry after C11-BODIPY staining in the indicated cells treated with cystine restriction. K Cell death was measured in the indicated cell lines and treated with cystine deficiency for 48 h. Error bars are mean ± SD. All P values were calculated using a two-tailed unpaired Student’s t-test. n ≥ 3 independent repeats unless specified. ns not significant (P > 0.05).