Hepatic resistance to cold ferroptosis in a mammalian hibernator Syrian hamster depends on effective storage of diet-derived α-tocopherol

Daisuke Anegawa, Yuki Sugiura, Yuta Matsuoka, Masamitsu Sone, Mototada Shichiri, Reo Otsuka, Noriko Ishida, Ken Ichi Yamada, Makoto Suematsu, Masayuki Miura, Yoshifumi Yamaguchi

Research output: Contribution to journalArticlepeer-review

Abstract

Mammalian hibernators endure severe and prolonged hypothermia that is lethal to non-hibernators, including humans and mice. The mechanisms responsible for the cold resistance remain poorly understood. Here, we found that hepatocytes from a mammalian hibernator, the Syrian hamster, exhibited remarkable resistance to prolonged cold culture, whereas murine hepatocytes underwent cold-induced cell death that fulfills the hallmarks of ferroptosis such as necrotic morphology, lipid peroxidation and prevention by an iron chelator. Unexpectedly, hepatocytes from Syrian hamsters exerted resistance to cold- and drug-induced ferroptosis in a diet-dependent manner, with the aid of their superior ability to retain dietary α-tocopherol (αT), a vitamin E analog, in the liver and blood compared with those of mice. The liver phospholipid composition is less susceptible to peroxidation in Syrian hamsters than in mice. Altogether, the cold resistance of the hibernator's liver is established by the ability to utilize αT effectively to prevent lipid peroxidation and ferroptosis.

Original languageEnglish
Pages (from-to)796
Number of pages1
JournalCommunications biology
Volume4
Issue number1
DOIs
Publication statusPublished - 2021 Jun 25

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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