ArticleCellular signalling2016
Iron depletion suppresses mTORC1-directed signalling in intestinal Caco-2 cells via induction of REDD1.
Article in Cellular signalling, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 53 citations in OpenAlex.
- Article
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- Inhibition of SLC11A1-Mediated Lysosomal Iron Accumulation in Microglia Promotes Repair Following White Matter Stroke.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The Prophylactic Protection ofMicroorganisms · 2025Article
- The Prophylactic Protection of Salmonella Typhimurium Infection by Lentilactobacillus buchneri GX0328-6 in Mice.Probiotics and antimicrobial proteins · 2024Article
- Regulation of translation in response to iron deficiency in human cells.Scientific reports · 2024Article
- Special Issue "Role of Apoptosis and Cellular Senescence in Cancer and Aging".International journal of molecular sciences · 2024Article
- Synephrine and Its Derivative Compound A: Common and Specific Biological Effects.International journal of molecular sciences · 2023Review
- Loss of miR-144/451 alleviates β-thalassemia by stimulating ULK1-mediated autophagy of free α-globin.Blood · 2023Article
- The stress-responsive protein REDD1 and its pathophysiological functions.Experimental & molecular medicine · 2023Review
- Role of iron in host-microbiota interaction and its effects on intestinal mucosal growth and immune plasticity in a piglet model.Science China. Life sciences · 2023Article
- Transferrin Receptor-Mediated Iron Uptake Promotes Colon Tumorigenesis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Mechanistic target of rapamycin (mTOR) regulates self-sustained quiescence, tumor indolence, and late clinical metastasis in a Beclin-1-dependent manner.Cell cycle (Georgetown, Tex.) · 2023Article
- Elevated transferrin receptor impairs T cell metabolism and function in systemic lupus erythematosus.Science immunology · 2023Article
- Up-Regulation of miR-9-5p Inhibits Hypoxia-Ischemia Brain Damage Through the DDIT4-Mediated Autophagy Pathways in Neonatal Mice.Drug design, development and therapy · 2023Article
- Nutritional Sensor REDD1 in Cancer and Inflammation: Friend or Foe?International journal of molecular sciences · 2022Review
- Chrysophanol Suppresses Cell Growth via mTOR/PPAR-α Regulation and ROS Accumulation in Cultured Human Tongue Squamous Carcinoma SAS Cells.Current issues in molecular biology · 2022Article
- TOR functions as a molecular switch connecting an iron cue with host innate defense against bacterial infection.PLoS genetics · 2021Article
- Reversing oncogenic transformation with iron chelation.Oncotarget · 2021Review
- Autophagy as a Target for Drug Development Of Skin Infection Caused by Mycobacteria.Frontiers in immunology · 2021Review
Corrections and comments
- Erratum issued
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Iron is an indispensable micronutrient that regulates many aspects of cell function, including growth and proliferation. These processes are critically dependent upon signalling via the mammalian or mechanistic target of rapamycin complex 1 (mTORC1). Herein, we test whether iron depletion induced by cell incubation with the iron chelator, deferoxamine (DFO), mediates its effects on cell growth through mTORC1-directed signalling and protein synthesis. We have used Caco-2 cells, a well-established in vitro model of human intestinal epithelia. Iron depletion increased expression of iron-regulated proteins (TfR, transferrin receptor and DMT1, divalent metal transporter, as predicted, but it also promoted a marked reduction in growth and proliferation of Caco-2 cells. This was strongly associated with suppressed mTORC1 signalling, as judged by reduced phosphorylation of mTOR substrates, S6K1 and 4E-BP1, and diminished protein synthesis. The reduction in mTORC1 signalling was tightly coupled with increased expression and accumulation of REDD1 (regulated in DNA damage and development 1) and reduced phosphorylation of Akt and TSC2. The increase in REDD1 abundance was rapidly reversed upon iron repletion of cells but was also attenuated by inhibitors of gene transcription, protein phosphatase 2A (PP2A) and by REDD1 siRNA--strategies that also antagonised the loss in mTORC1 signalling associated with iron depletion. Our findings implicate REDD1 and PP2A as crucial regulators of mTORC1 activity in iron-depleted cells and indicate that their modulation may help mitigate atrophy of the intestinal mucosa that may occur in response to iron deficiency.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.