The Chemistry and Biology of Ferroptosis

Cell Chem Biol. 2020 Apr 16;27(4):365-375. doi: 10.1016/j.chembiol.2020.03.013.


Ferroptosis is a recently described form of cell death driven by iron-dependent lipid peroxidation. This type of cell death was first observed in response to treatment of tumor cells with a small-molecule chemical probe named erastin. Most subsequent advances in understanding the mechanisms governing ferroptosis involved the use of genetic screens and small-molecule probes. We describe herein the utility and limitations of chemical probes that have been used to analyze and perturb ferroptosis, as well as mechanistic studies of ferroptosis that benefitted from the use of these probes and genetic screens. We also suggest probes for ferroptosis and highlight mechanistic questions surrounding this form of cell death that will be a high priority for exploration in the future.

Keywords: ROS; cancer; cell death; chemical probe; cysteine; ferroptosis; glutathione; iron; lipid peroxidation; metabolism.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Amino Acid Transport System y+ / antagonists & inhibitors
  • Amino Acid Transport System y+ / metabolism
  • Energy Metabolism
  • Ferroptosis*
  • Humans
  • Iron / metabolism
  • Lipid Peroxidation
  • Molecular Probes / chemistry*
  • Molecular Probes / metabolism
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Phospholipid Hydroperoxide Glutathione Peroxidase / antagonists & inhibitors
  • Phospholipid Hydroperoxide Glutathione Peroxidase / metabolism
  • Signal Transduction


  • Amino Acid Transport System y+
  • Molecular Probes
  • SLC7A11 protein, human
  • Iron
  • Phospholipid Hydroperoxide Glutathione Peroxidase