title: Mammalian target of rapamycin coordinates iron metabolism with iron-sulfur cluster assembly enzyme and tristetraprolin.
abstract: Both iron deficiency and excess are relatively common health concerns. Maintaining the body's levels of iron within precise boundaries is critical for cell functions. However, the difference between iron deficiency and overload is often a question of a scant few milligrams of iron. The mammalian target of rapamycin (mTOR), an atypical Ser/Thr protein kinase, is attracting significant amounts of interest due to its recently described role in iron homeostasis. Despite extensive study, a complete understanding of mTOR function has remained elusive. mTOR can form two multiprotein complexes that consist of mTOR complex 1 (mTORC1) and mTOR complex 2. Recent advances clearly demonstrate that mTORC1 can phosphorylate iron-sulfur cluster assembly enzyme ISCU and affect iron-sulfur clusters assembly. Moreover, mTOR is reported to control iron metabolism through modulation of tristetraprolin expression. It is now well appreciated that the hormonal hepcidin-ferroportin system and the cellular iron-responsive element/iron-regulatory protein regulatory network play important regulatory roles for systemic iron metabolism. Sustained ISCU protein levels enhanced by mTORC1 can inhibit iron-responsive element and iron-regulatory protein binding activities. In this study, hepcidin gene and protein expression in the livers of tristetraprolin knockout mice were dramatically reduced. Here, we highlight and summarize the current understanding of how mTOR pathways serve to modulate iron metabolism and homeostasis as the third iron-regulatory system.
authors: Key Laboratory of Animal Physiology, Biochemistry and Molecular Biology of Hebei Province, Hebei Normal University, Hebei Province, China.
authors: Peng
authors: P
authors: Guan
authors: Key Laboratory of Animal Physiology, Biochemistry and Molecular Biology of Hebei Province, Hebei Normal University, Hebei Province, China; School of Basic Medical Sciences, Hebei University of Traditional Chinese Medicine, Hebei Province, China. Electronic address: Wangna9@tom.com.
authors: Na
authors: N
authors: Wang
mesh_terms: D000818:Animals; D006706:Homeostasis; D006801:Humans; D007501:Iron / Q000378:metabolism*; D019189:Iron Metabolism Disorders / Q000378:metabolism*; D007506:Iron-Sulfur Proteins / Q000378:metabolism*; D000076222:Mechanistic Target of Rapamycin Complex 1; D046912:Multiprotein Complexes / Q000378:metabolism; D013455:Sulfur / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D051816:Tristetraprolin / Q000378:metabolism*
chemical_list: D007506:Iron-Sulfur Proteins; D046912:Multiprotein Complexes; D051816:Tristetraprolin; D013455:Sulfur; D007501:Iron; C546842:MTOR protein, human; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases
keywords: Iron; Iron-sulfur clusters; Rapamycin; Transferrin receptor; Tristetraprolin