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

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

研究成果: ジャーナルへの寄稿記事

70 引用 (Scopus)

抄録

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.

元の言語英語
ページ(範囲)339-351
ページ数13
ジャーナルCell metabolism
14
発行部数3
DOI
出版物ステータス出版済み - 9 7 2011

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Iron Regulatory Protein 2
Iron
Liver
Homeostasis
Acute Liver Failure
Fatty Liver
Proteolysis
Maintenance
Diet

All Science Journal Classification (ASJC) codes

  • Physiology
  • Molecular Biology
  • Cell Biology

これを引用

The FBXL5-IRP2 axis is integral to control of iron metabolism in vivo. / Moroishi, Toshiro; Nishiyama, Masaaki; Takeda, Yukiko; Iwai, Kazuhiro; Nakayama, Keiichi I.

:: Cell metabolism, 巻 14, 番号 3, 07.09.2011, p. 339-351.

研究成果: ジャーナルへの寄稿記事

Moroishi, Toshiro ; Nishiyama, Masaaki ; Takeda, Yukiko ; Iwai, Kazuhiro ; Nakayama, Keiichi I. / The FBXL5-IRP2 axis is integral to control of iron metabolism in vivo. :: Cell metabolism. 2011 ; 巻 14, 番号 3. pp. 339-351.
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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.",
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AU - Nakayama, Keiichi I.

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