ROS-mediated autophagy increases intracellular iron levels and ferroptosis by ferritin and transferrin receptor regulation

Abstract Ferroptosis is a novel form of programmed cell death in which the accumulation of intracellular iron promotes lipid peroxidation, leading to cell death. Recently, the induction of autophagy has been suggested during ferroptosis. However, this relationship between autophagy and ferroptosis is still controversial and the autophagy-inducing mediator remains unknown. In this study, we confirmed that autophagy is indeed induced by the ferroptosis inducer erastin. Furthermore, we show that autophagy leads to iron-dependent ferroptosis by degradation of ferritin and induction of transferrin receptor 1 (TfR1) expression, using wild-type and autophagy-deficient cells, BECN1 +/− and LC3B −/− . Consistently,…

• NR
  National Research Foundation

  Award: 2014R1A6A1030318
• NR
  National Research Foundation of Korea

  Award: 2014R1A6A1030318