Involvement of ferroptosis in human motor neuron cell death

Tsuyoshi Matsuo, Keiko Adachi-Tominari, Osamu Sano, Takayuki Kamei, Masahiro Nogami, Kazuhiro Ogi, Hideyuki Okano, Masato Yano

Research output: Contribution to journalArticlepeer-review

Abstract

Ferroptosis was recently defined as a novel type of programmed cell death depending on iron and lipid peroxidation. It is biologically different from other types of cell death such as apoptosis. While the involvement of ferroptosis in cancer, patient and animal model have been intensely studied, ferroptosis in human motor neuron model is still clearly unknown. Here we carefully assessed ferroptosis using human iPS cell-derived motor neuron (hiMNs). We found that almost all hiMNs died by the treatment of glutathione peroxidase 4 (GPX4) inhibitors. Importantly, the cell death was rescued by one antioxidant, vitamin E acetate, iron chelators and lipid peroxidase inhibitors with high dynamic ranges. Finally, these data clearly indicated that ferroptosis constitutively occurs in hiMNs, suggesting the possibility that it might play a biologically and pathologically important roles in motor neuron death such as motor neuron disease (MND)/Amyotrophic lateral sclerosis (ALS).

Original languageEnglish
Pages (from-to)24-29
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume566
DOIs
Publication statusPublished - 2021 Aug 20

Keywords

  • Amyotrophic lateral sclerosis
  • Cell death
  • Ferroptosis
  • Glutathione peroxidase 4
  • Human motor neuron
  • iPS cell

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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