A graphical journey through iron metabolism, microRNAs, and hypoxia in ferroptosis

Redox Biol. 2022 Aug:54:102365. doi: 10.1016/j.redox.2022.102365. Epub 2022 Jun 9.

Abstract

Ferroptosis is an iron-dependent form of cell death, which is triggered by disturbed membrane integrity due to an overproduction of lipid peroxides. Induction of ferroptosis comprises several alterations, i.e. altered iron metabolism, response to oxidative stress, or lipid peroxide production. At the physiological level transcription, translation, and microRNAs add to the appearance and/or activity of building blocks that negatively or positively balance ferroptosis. Ferroptosis contributes to tissue damage in the case of, e.g., brain and heart injury but may be desirable to overcome chemotherapy resistance. For a more complete picture, it is crucial to also consider the cellular microenvironment, which during inflammation and in the tumor context is dominated by hypoxia. This graphical review visualizes basic mechanisms of ferroptosis, categorizes general inducers and inhibitors of ferroptosis, and puts a focus on microRNAs, iron homeostasis, and hypoxia as regulatory components.

Keywords: Cancer; Cell death; Erythrophagocytosis; Lipid peroxidation; Mitochondria.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Ferroptosis* / genetics
  • Humans
  • Hypoxia / genetics
  • Iron / metabolism
  • Lipid Peroxidation
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism

Substances

  • MicroRNAs
  • Iron