mTOR Regulates Cellular Iron Homeostasis through Tristetraprolin

作者：Bayeva Marina; Khechaduri Arineh; Puig Sergi; Chang Hsiang Chun; Patial Sonika; Blackshear Perry J; Ardehali Hossein^*

来源：Cell Metabolism, 2012, 16(5): 645-657.

DOI：10.1016/j.cmet.2012.10.001

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.

• 出版日期2012-11-7
• 单位西北大学