Fig. 5: ACSL4-mediated lipid metabolism and ferroptosis sensitivity are regulated by BAP1.
A Principal components analysis of indicated cell lines. B Heatmaps depicting the changes in the composition of each lipid subclass within the indicated cell lines. C Volcano plots representing lipidomic data from the indicated cell lines. The red and green dots represent lipid metabolites with at least 1-fold increase or decrease in indicated cells (P < 0.05). D Venn diagram illustrating the overlap of 679 BAP1/ACSL4-dependent metabolites between 932 and 929 differentially expressed metabolites (FC > 1, P < 0.05) in different comparison groups in UMRC6 cells. E KEGG enrichment bar plot of metabolism-related pathways for 679 metabolites. GPI Glycosylphosphatidylinositol. Bar graph showing lipid abundance of PL-PUFA1s (F) and PL-PUFA2s (G) in UMRC6-BAP1 and ACSL4-KO UMRC6 cells restored with BAP1-WT. Bar graph showing lipid abundance of 15-oxoETE (H), ( ± )5-HETE (I), and (±)15-HETE (J) in indicated cells. K Illustration of the ACSL4-mediated lipid metabolism regulation pathway. Cell death was measured in BAP1 OE UMRC6 cells lacking ACSL4 treated with cystine limitation (L) or TBH (10 μM) (M) combined with AA (1 μM) or AA-CoA (1 μM) for 6 h. Lipid peroxidation was assessed by flow cytometry after C11-BODIPY staining in indicated cells treated with cystine-free (N) or TBH (O) combined with AA or AA-CoA. 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.
