The FBXL5-IRP2 axis is integral to control of iron metabolism in vivo

Toshiro Moroishi, Masaaki Nishiyama, Yukiko Takeda, Kazuhiro Iwai, Keiichi I. Nakayama

Research output: Contribution to journalArticlepeer-review

85 Citations (Scopus)

Abstract

Iron-dependent degradation of iron-regulatory protein 2 (IRP2) is a key event for maintenance of an appropriate intracellular concentration of iron. Although FBXL5 (F box and leucine-rich repeat protein 5) is thought to mediate this degradation, the role of FBXL5 in the control of iron homeostasis in vivo has been poorly understood. We have now found that mice deficient in FBXL5 died in utero, associated with excessive iron accumulation. This embryonic mortality was prevented by additional ablation of IRP2, suggesting that impaired IRP2 degradation is primarily responsible for the death of Fbxl5 - /- mice. We also found that liver-specific deletion of Fbxl5 resulted in deregulation of both hepatic and systemic iron homeostasis, leading to the development of steatohepatitis. The liver-specific mutant mice died with acute liver failure when fed a high-iron diet. Thus, our results uncover a major role for FBXL5 in ensuring an appropriate supply of iron to cells.

Original languageEnglish
Pages (from-to)339-351
Number of pages13
JournalCell metabolism
Volume14
Issue number3
DOIs
Publication statusPublished - Sep 7 2011

All Science Journal Classification (ASJC) codes

  • Physiology
  • Molecular Biology
  • Cell Biology

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