Extended Data Fig. 7: FH inhibition triggers the NRF2 and ATF4 stress response and promotes GDF15 release.
From: Macrophage fumarate hydratase restrains mtRNA-mediated interferon production
a, Heatmap of significantly differentially expressed RNA seq data in BMDMs pre-treated with FHIN1 compared to DMSO control (n = 3; LPS 4 h). Volcano plots of proteomics in BMDMs pre-treated with DMSO, FHIN1 (b) or DMF (c) (n = 5; LPS 4 h). d, ELISA of GDF15 in BMDMs pre-treated with DMSO or FHIN1 (n = 3; LPS 4 h). e, Nrf2 expression or ATF4 protein levels after silencing of Nrf2 or Atf4, respectively, in BMDMs pre-treated with DMSO or FHIN1 (n = 6; LPS 4 h). f, Gdf15 expression after silencing of Nrf2 or Atf4 respectively in BMDMs pre-treated with DMSO or FHIN1 (n = 3, LPS 4 h; FHIN1/Nrf2 RNAi (P = 0.000048)). d-f, Data are mean ± s.e.m. e, 1 representative blot of 6 shown. n = biological replicates unless stated otherwise. P values calculated using one-way ANOVA for multiple comparisons.
