Fig. 2: TFEB stimulates methionine cycle-transsulfuration to increase hepatic cysteine and GSH pool.

a Illustration of methionine cycle-transsulfuration pathway and GSH and taurine synthesis. MAT1A Methionine adenosyltransferase 1A, CBS cystathionine β-synthase, CSE cystathionine γ lyase, SAMe S-adenosylmethionine, SAH S-adenosylhomocysteine, BHMT betaine-homocysteine S-methyltransferase, CDO1 cysteine dioxygenase 1, CSAD cysteine sulfinic acid decarboxylase, GCL glutamate cysteine ligase, GCLC glutamate cysteine ligase catalytic subunit, GCLM glutamate cysteine ligase modifier subunit, CSA cysteine sulfinic acid, H–M cycle homocysteine–methionine cycle, DMG dimethylglycine. GSH: reduced glutathione. b, c, d Male 10 weeks old C57BL/6 J mice were intravenously injected with Ad-Null or Ad-TFEB at 5 × 10⁸ pfu/mouse. One week later, mice were fed chow (C) or Western diet (WD) for one additional week. Relative abundance of liver metabolites is shown with control arbitrarily set as 1. Results are mean ± SEM (n = 4). e Western blot of liver protein expression in mice. Each band represents an individual mouse sample. f, g Male 10 weeks old C57BL/6 J mice were intravenously injected with Ad-Null or Ad-TFEB at 5 × 10⁸ pfu/mouse. One week later, mice were fed chow (C) or Western diet (WD) for one additional week. Relative abundance of liver metabolites is shown with control arbitrarily set as 1. Results are mean ± SEM (n = 4). Detailed statistical analysis of (b, c, d, f, g) is described under Metabolomics, statistical and bioinformatics analysis in the Methods section. A p value < 0.05 is considered statistically significant. Source data for (b, c, d, e, f, g) are provided as a Source Data file.