mTOR regulates cellular iron homeostasis through tristetraprolin
Open accessAbstract
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.
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Rapamycin treatment may lead to autophagic degradation of TfR1 or modulate levels by enhancing degradation of TfR1 mRNA.
“Additionally, rapamycin treatment may lead to autophagic degradation of TfR1 or modulate levels by enhancing degradation of TfR1 mRNA [78].”
From Iron accumulation in senescent cells is coupled with impaired ferritinophagy and inhibition of ferroptosis (2018) · cites this paper as [78]
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References 41 · Cited by 197
Research works printed but not linked: 1
- WHO Worldwide prevalence of anaemia 1993–2005 2008 Geneva, Switzerland WHO Press
- Authors
- Bayeva, M., Khechaduri, A., Puig, S., Chang, H.-C., Patial, S., Blackshear, P. J., & Ardehali, H.
- Affiliations
- Northwestern University (US)
- Consejo Superior de Investigaciones Científicas (ES)
- National Institutes of Health (US)
- Corresponding author
- Ardehali, Hossein
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2012-11
- Volume
- 16
- Issue
- 5
- Pages
- 645-657
- ISSN
- 1550-4131 (ISSN-L)
- PMC
- PMC3594686
- OpenAlex
- W2023483654
- Cited by
- 197
- References
- 41
- Citations by year
- 2026: 10 · 2025: 18 · 2024: 22 · 2023: 26 · 2022: 21 · 2021: 19 · 2020: 13 · 2019: 11 · 2018: 15 · 2017: 16 · 2016: 9 · 2015: 2 · 2014: 8 · 2013: 5 · 2012: 2
- FWCI
- 3.62
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Civil War Book Review (submittedVersion)
- Funders
- National Institutes of Health (1p01hl108795-01)
- National Heart, Lung, and Blood Institute (P01-HL-108795, K02HL107448, R01HL104181, R01HL087149)
- National Cancer Institute (CA 060553, P30CA060553)
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Ferroptosis and cancer prognosis
- Health Sciences › Nursing › Nutrition and Dietetics › Trace Elements in Health
- Keywords
- mTOR, tristetraprolin, cellular iron homeostasis, transferrin receptor 1, mRNA stability, iron chelation, iron regulatory proteins, inflammation
- MeSH terms
- Tuberous Sclerosis Complex 2 Protein, Animals, Cell Line, DNA-Binding Proteins, Iron, Receptors, Transferrin, RNA, Messenger, Saccharomyces cerevisiae, Transcription Factors, Gene Expression, Sirolimus, Tumor Suppressor Proteins, Saccharomyces cerevisiae Proteins, RNA Interference, RNA, Small Interfering, Mice, Tristetraprolin, TOR Serine-Threonine Kinases
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