Fig. 2: Aspartate is a RIPK1-dependent metabolite under starvation.

a Volcano plot of metabolites in WT and Ripk1^−/− MEFs under normal culture conditions. P values were determined by a two-tailed Student’s t-test. Red dots indicate significantly changed metabolites (p < 0.05 and fold change >1.2, n = 6 biologically independent samples in each group). b Pathway enrichment analysis of significantly changed metabolites in MEFs in (a). c Relative abundances of metabolites in the alanine, aspartate, and glutamate metabolism pathway were measured in MEFs. n = 6 biologically independent samples in each group. P values were determined by a two-tailed Student’s t-test. d, e Metabolites were significantly increased/decreased in Ripk1^−/− group compared with WT group (p < 0.05), and significantly rescued (p < 0.05) in Ripk1^−/− + Ripk1 group compared with Ripk1^−/− group: MEFs (d, WT group, n = 9; Ripk1^−/− group, n = 10; Ripk1^−/− + Ripk1 group, n = 10); Jurkat cells (e, n = 7). All cells were cultured in EBSS for 4 h. All numbers are biologically independent samples. P values were determined by a two-tailed Student’s t-test with FDR correction. f, g Metabolites were significantly (p < 0.05) increased/decreased in Ripk1^−/− compared with WT, and significantly rescued (p < 0.05) in Ripk1^+/− compared with Ripk1^−/− in mouse liver (f, n = 6 biologically independent samples) and brain (g, WT group, n = 6; Ripk1^−/− group, n = 5; Ripk1^−/− +  Ripk1 group, n = 6) under starvation. All numbers are biologically independent samples. P values were determined by a two-tailed Student’s t-test with FDR correction. Bar graphs represent mean ± SEM.