Fig. 6: ZEB1 inhibits mitochondrial protein translation by restricting amino acid transport.

a GSEA plot “Amino acid transport” signature in Zeb1^WT macrophages under the indicated treatments. b Slc7a8 mRNA in macrophages from Zeb1^WT and Zeb1^∆M mice subjected to the indicated treatments. Average of 4–10 mice per genotype and condition in three independent experiments (n = 8,8,7,8,4,5,7,5). c Representative blot of five independent experiments for SLC7A8 and GAPDH in peritoneal macrophages under the indicated treatments. Quantification of SLC7A8 relative to GAPDH (n = 5). d Glucose uptake by peritoneal macrophages from Zeb1^WT and Zeb1^∆M treated as indicated and assessed 4 h after the last LPS dose (n = 5). e As in (d), but for glutamine uptake (n = 4). f As in (d), but for intracellular BCAAs in cell lysates 4 h after the last LPS dose (n = 6). g As in (f), but for intracellular glutamine (n = 7) and glutamate (n = 8) levels corrected by cell protein levels. h Relative mtDNA copy number in macrophages from Zeb1^WT and Zeb1^∆M mice treated as indicated and cultured with (left panel) or without (right panel) glutamine in the medium (n = 5). i Western blots for p70S6K, P-P70S6K, and GAPDH in Zeb1^WT and Zeb1^∆M peritoneal macrophages treated as indicated. A representative blot and quantification of P-p70s6k normalized to p70s6k (n = 4). (j) Western blots for for P-p70s6k, P70S6K, IL6, SLC7A8, and GAPDH in PBMCs of three healthy donors and three septic patients at 0 and 72 h. Representative blot of two independent experiments, with 2-3 patients per condition. Quantification of P-p70s6k protein levels normalized to p70s6k (n = 6), as well as IL6 (n = 7) and SLC7A8 (n = 5) normalized to GAPDH. k ZEB1 mRNA in PBMCs from septic patients at 0 h (n = 11) and 72 h (n = 10), healthy donors (n = 10), and PsA patients (n = 8). l As in (k), but for SQSTM1 in septic patients (n = 9,5) and Healthy/PsA (n = 6), IL4 in septic patients (n = 12,10) and Healthy/PsA (n = 10,9), IL6 in septic patients (n = 8,4) and Healthy/PsA (n = 4,7), SLC2A1 in septic patients (n = 11) and Healthy/PsA (n = 10), and SLC7A8 in septic patients (n = 9,11) and Healthy/PsA (n = 8). Graph bars in Fig. 6 represent mean values +/− SEM with two-tailed unpaired Mann–Whitney test. p ≤ 0.001 (***), p ≤ 0.01 (**) or p ≤ 0.05 (*) levels, or non-significant (ns) for values of p > 0.05. Raw data along p values for statistical analyses are included in the Source Data file.