Ferroptosis: Death by Lipid Peroxidation

Trends Cell Biol. 2016 Mar;26(3):165-176. doi: 10.1016/j.tcb.2015.10.014. Epub 2015 Dec 2.


Ferroptosis is a regulated form of cell death driven by loss of activity of the lipid repair enzyme glutathione peroxidase 4 (GPX4) and subsequent accumulation of lipid-based reactive oxygen species (ROS), particularly lipid hydroperoxides. This form of iron-dependent cell death is genetically, biochemically, and morphologically distinct from other cell death modalities, including apoptosis, unregulated necrosis, and necroptosis. Ferroptosis is regulated by specific pathways and is involved in diverse biological contexts. Here we summarize the discovery of ferroptosis, the mechanism of ferroptosis regulation, and its increasingly appreciated relevance to both normal and pathological physiology.

Keywords: GPX4; ROS; cell death; ferroptosis; lipid peroxides; system x(c)(−).

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Death / physiology
  • Glutamic Acid / physiology
  • Glutathione Peroxidase / physiology
  • Humans
  • Iron / physiology
  • Lipid Peroxidation*
  • Neurons / physiology
  • Phospholipid Hydroperoxide Glutathione Peroxidase
  • Reactive Oxygen Species / metabolism


  • Reactive Oxygen Species
  • Glutamic Acid
  • Iron
  • Phospholipid Hydroperoxide Glutathione Peroxidase
  • Glutathione Peroxidase