Cystine and Methionine Deficiency Promotes Ferroptosis by Inducing B-Cell Translocation Gene 1.

ABSTRACT: Ferroptosis is a type of programmed necrosis triggered by iron-dependent lipid peroxidation. We investigated the role of B-cell translocation gene 1 (BTG1) in cystine and methionine deficiency (CST/Met (-))-mediated cell death. CST/Met (-) depleted reduced and oxidized glutathione in hepatocyte-derived cells, increased prostaglandin-endoperoxide synthase 2 expression, and promoted reactive oxygen species accumulation and lipid peroxidation, as well as necrotic cell death. CST/Met (-)-mediated cell death and lipid peroxidation was specifically inhibited by pretreatment with ferroptosis inhibitors. In parallel with cell death, CST/Met (-) blocked global protein translation and increased the expression of genes associated with the integrated stress response. Moreover, CST/Met (-) significantl

SUBMITTER: Cho IJ 

PROVIDER: S-EPMC8532826 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature