Ferroptosis is an autophagic cell death process Academic Article uri icon


MeSH Major

  • Gene Expression Regulation
  • Immunoglobulin J Recombination Signal Sequence-Binding Protein
  • MicroRNAs
  • Osteoclasts
  • Osteogenesis
  • Tumor Necrosis Factor-alpha


  • Ferroptosis is an iron-dependent form of regulated necrosis. It is implicated in various human diseases, including ischemic organ damage and cancer. Here, we report the crucial role of autophagy, particularly autophagic degradation of cellular iron storage proteins (a process known as ferritinophagy), in ferroptosis. Using RNAi screening coupled with subsequent genetic analysis, we identified multiple autophagy-related genes as positive regulators of ferroptosis. Ferroptosis induction led to autophagy activation and consequent degradation of ferritin and ferritinophagy cargo receptor NCOA4. Consistently, inhibition of ferritinophagy by blockage of autophagy or knockdown of NCOA4 abrogated the accumulation of ferroptosis-associated cellular labile iron and reactive oxygen species, as well as eventual ferroptotic cell death. Therefore, ferroptosis is an autophagic cell death process, and NCOA4-mediated ferritinophagy supports ferroptosis by controlling cellular iron homeostasis.

publication date

  • September 2016



  • Academic Article



  • eng

PubMed Central ID

  • PMC5034113

Digital Object Identifier (DOI)

  • 10.1038/cr.2016.95

PubMed ID

  • 27514700

Additional Document Info

start page

  • 1021

end page

  • 32


  • 26


  • 9