articleProceedings of the National Academy of SciencesAug 9, 2016BRONZE OA

Peroxidation of polyunsaturated fatty acids by lipoxygenases drives ferroptosis

WSWan Seok YangKJKatherine J. KimMMMichael M. GaschlerMMMilesh M. PatelMSMikhail S. Shchepinov

St. John's University · Columbia University · +2 more institutions

PubMed
Indexed incrossrefpubmed

Abstract

Ferroptosis is form of regulated nonapoptotic cell death that is involved in diverse disease contexts. Small molecules that inhibit glutathione peroxidase 4 (GPX4), a phospholipid peroxidase, cause lethal accumulation of lipid peroxides and induce ferroptotic cell death. Although ferroptosis has been suggested to involve accumulation of reactive oxygen species (ROS) in lipid environments, the mediators and substrates of ROS generation and the pharmacological mechanism of GPX4 inhibition that generates ROS in lipid environments are unknown. We report here the mechanism of lipid peroxidation during ferroptosis, which involves phosphorylase kinase G2 (PHKG2) regulation of iron availability to lipoxygenase…

Citation impact

2,251
total citations
FWCI
45.24
Percentile
100%
References
60
Citations per year

Authors

6

Topics & keywords

Topics
Keywords
  • GPX4
  • Phospholipid-hydroperoxide glutathione peroxidase
  • Lipid peroxidation
  • Reactive oxygen species
  • Programmed cell death
  • Biochemistry
  • Chemistry
  • Phospholipid
No related works found for this paper.

Funding