Fig. 5: The ISR alters the cellular lipidome and drives LD formation to promote cell survival during stress. | Nature Communications

Fig. 5: The ISR alters the cellular lipidome and drives LD formation to promote cell survival during stress.

From: Specific activation of the integrated stress response uncovers regulation of central carbon metabolism and lipid droplet biogenesis

Fig. 5

a Heatmap of lipid abundances in Dmr-PERK cells treated for the indicated amount of time with dimerizer (0.05 nM). Columns show three technical replicate measurements for each time point, grouped by lipid class. Measurements are normalized to the mean abundance at t = 0 on a log2 scale. Color bars indicate triglycerides (TG), cholesterol esters (CE), diacylglycerides (DG), glycerophospholipids (GPL), plasmalogens, sphingolipids and other lipid species. b Schematic of the lipid synthesis pathways that supply the constituents of lipid droplets. Enzymes mediating each step are labeled in gray. c BODIPY labeled Dmr-PERK cells treated for 8 h with vehicle (Veh) or dimerizer (Dmr, 1 nM). Scale bar = 5 μm d Quantification of the number of LD per cell in Dmr-PERK cells treated for 8 h with vehicle (Veh.) or the indicated concentration of dimerizer (Dmr). Median with interquartile range is indicated. 240 cells were quantified per condition. Statistical significance was evaluated by one-way ANOVA followed by Dunnett’s multiple comparison test. e Quantification of the number of LD in Dmr-PERK cells at the indicated time points following treatment with the indicated concentration of dimerizer. Error bars show mean ± SD per well across three independent experiments. f, g Bar plots representing the mean number of LD per cell per well in Dmr-PERK cells treated for 8 h with dimerizer (Dmr, 1 nM), ACATi (10 μM), DGAT1/2i (20 μM each) or ACCi (2 μg/mL) as indicated. Error bars show mean ± SD across three independent experiments. Statistical significance was evaluated by one-way ANOVA followed by Dunnett’s multiple comparison test. h Quantification of the percent confluence of Dmr-PERK cells treated with vehicle, dimerizer (Dmr, 0.024 nM), ACATi (10 μM), DGAT1/2i (20 μM each) or ACCi (2 μg/mL), as indicated. Error bars show mean ± SD of two technical replicates and is representative of three independent experiments. Source data are provided as a Source Data file.

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