The Mechanisms of Ferroptosis Under Hypoxia

Cell Mol Neurobiol. 2023 Oct;43(7):3329-3341. doi: 10.1007/s10571-023-01388-8. Epub 2023 Jul 17.

Abstract

Ferroptosis is a new form of programmed cell death, which is characterized by the iron-dependent accumulation of lipid peroxidation and increase of ROS, resulting in oxidative stress and cell death. Iron, lipid, and multiple signaling pathways precisely control the occurrence and implementation of ferroptosis. The pathways mainly include Nrf2/HO-1 signaling pathway, p62/Keap1/Nrf2 signaling pathway. Activating p62/Keap1/Nrf2 signaling pathway inhibits ferroptosis. Nrf2/HO-1 signaling pathway promotes ferroptosis. Furthermore, some factors also participate in the occurrence of ferroptosis under hypoxia, such as HIF-1, NCOA4, DMT1. Meanwhile, ferroptosis is related with hypoxia-related diseases, such as MIRI, cancers, and AKI. Accordingly, ferroptosis appears to be a therapeutic target for hypoxia-related diseases.

Keywords: Ferroptosis; Hypoxia; Hypoxia-inducible factor; Lipid peroxidation; System Xc.

Publication types

  • Review

MeSH terms

  • Ferroptosis*
  • Humans
  • Hypoxia
  • Iron
  • Kelch-Like ECH-Associated Protein 1
  • NF-E2-Related Factor 2
  • Reactive Oxygen Species

Substances

  • Kelch-Like ECH-Associated Protein 1
  • NF-E2-Related Factor 2
  • Iron
  • Reactive Oxygen Species