mTOR Regulates Cellular Iron Homeostasis through Tristetraprolin

被引：160

作者：

Bayeva, Marina ^{[1
]}

Khechaduri, Arineh ^{[1
]}

Puig, Sergi ^{[2
]}

Chang, Hsiang-Chun ^{[1
]}

Patial, Sonika ^{[3
]}

Blackshear, Perry J. ^{[3
]}

Ardehali, Hossein ^{[1
]}

机构：

[1] Northwestern Univ, Sch Med, Feinberg Cardiovasc Res Inst, Chicago, IL 60611 USA

[2] CSIC, Inst Agroquim & Tecnol Alimentos, Dept Biotecnol, Valencia 46100, Spain

[3] NIEHS, Lab Signal Transduct, Res Triangle Pk, NC 27709 USA

来源：

CELL METABOLISM | 2012年 / 16卷 / 05期

关键词：

MESSENGER-RNA DEGRADATION; SIGNALING PATHWAY; MAMMALIAN TARGET; DEFICIENCY; METABOLISM; PROTEIN; CELLS; SIROLIMUS; DISEASE; ALPHA;

D O I：

10.1016/j.cmet.2012.10.001

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Iron is an essential cofactor with unique redox properties. Iron-regulatory proteins 1 and 2 (IRP1/2) have been established as important regulators of cellular iron homeostasis, but little is known about the role of other pathways in this process. Here we report that the mammalian target of rapamycin (mTOR) regulates iron homeostasis by modulating transferrin receptor 1 (TfR1) stability and altering cellular iron flux. Mechanistic studies identify tristetraprolin (TTP), a protein involved in anti-inflammatory response, as the downstream target of mTOR that binds to and enhances degradation of TfR1 mRNA. We also show that TTP is strongly induced by iron chelation, promotes downregulation of iron-requiring genes in both mammalian and yeast cells, and modulates survival in low-iron states. Taken together, our data uncover a link between metabolic, inflammatory, and iron-regulatory pathways, and point toward the existence of a yeast-like TTP-mediated iron conservation program in mammals.

引用

页码：645 / 657

页数：13

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