ATF3 promotes erastin-induced ferroptosis by suppressing system Xc–

Abstract The amino acid antiporter system Xc − is important for the synthesis of glutathione (GSH) that functions to prevent lipid peroxidation and protect cells from nonapoptotic, iron-dependent death (i.e., ferroptosis). While the activity of system Xc − often positively correlates with the expression level of its light chain encoded by SLC7A11 , inhibition of system Xc − activity by small molecules (e.g., erastin) causes a decrease in the intracellular GSH level, leading to ferroptotic cell death. How system Xc − is regulated during ferroptosis remains largely unknown. Here we report that activating transcription factor 3 (ATF3), a common stress sensor, can promote ferroptosis induced by erastin. ATF3…

• NI
  National Institutes of Health

  Awards: R01CA139107, R01CA190429
• NC
  National Cancer Institute

  Award: RO1CA190429
• DO
  Division of Cancer Epidemiology and Genetics, National Cancer Institute

  Award: RO1CA139107