Ferritinophagy and Ferroptosis in Cerebral Ischemia Reperfusion Injury

Neurochem Res. 2024 Aug;49(8):1965-1979. doi: 10.1007/s11064-024-04161-5. Epub 2024 Jun 4.


Cerebral ischemia-reperfusion injury (CIRI) is the second leading cause of death worldwide, posing a huge risk to human life and health. Therefore, investigating the pathogenesis underlying CIRI and developing effective treatments are essential. Ferroptosis is an iron-dependent mode of cell death, which is caused by disorders in iron metabolism and lipid peroxidation. Previous studies demonstrated that ferroptosis is also a form of autophagic cell death, and nuclear receptor coactivator 4(NCOA4) mediated ferritinophagy was found to regulate ferroptosis by interfering with iron metabolism. Ferritinophagy and ferroptosis are important pathogenic mechanisms in CIRI. This review mainly summarizes the link and regulation between ferritinophagy and ferroptosis and further discusses their mechanisms in CIRI. In addition, the potential treatment methods targeting ferritinophagy and ferroptosis for CIRI are presented, providing new ideas for the prevention and treatment of clinical CIRI in the future.

Keywords: Cerebral ischemia–reperfusion injury; Ferritinophagy; Ferroptosis; Iron metabolism; NCOA4.

Publication types

  • Review

MeSH terms

  • Animals
  • Autophagic Cell Death
  • Brain Ischemia / metabolism
  • Brain Ischemia / pathology
  • Ferritins* / metabolism
  • Ferroptosis* / physiology
  • Humans
  • Iron / metabolism
  • Lipid Peroxidation / physiology
  • Nuclear Receptor Coactivators / metabolism
  • Reperfusion Injury* / metabolism
  • Reperfusion Injury* / pathology


  • Ferritins
  • Iron
  • Nuclear Receptor Coactivators
  • NCOA4 protein, human