Regulation of translation in response to iron deficiency in human cells

Protein synthesis is a highly energy-consuming process that is downregulated in response to many environmental stresses or adverse conditions. Studies in the yeast Saccharomyces cerevisiae have shown that bulk translation is inhibited during adaptation to iron deficiency, which is consistent with its requirement for ribosome biogenesis and recycling. Although iron deficiency anemia is the most common human nutritional disorder, how iron modulates translation in mammals is poorly understood. Studies during erythropoiesis have shown that iron bioavailability is coordinated with globin synthesis via bulk translation regulation. However, little is known about the control of translation during iron limitation in other tissues. Here, we investigated how iron depletion affects protein synthesis in human osteosarcoma U-2 OS cells. By adding an extracellular iron chelator, we observed that iron deficiency limits cell proliferation, induces autophagy, and decreases the global rate of protein synthesis. Analysis of specific molecular markers indicates that the inhibition of bulk translation upon iron limitation occurs through the eukaryotic initiation factor eIF2α and mechanistic target of rapamycin (mTOR) pathways. In contrast to other environmental and nutritional stresses, iron depletion does not trigger the assembly of messenger ribonucleoprotein stress granules, which typically form upon polysome disassembly.

Bibliographic Details

Main Authors:	Puig Segui, Mireia S., Decker, Carolyn J., Barlit, Hanna, Labunskyy, Vyacheslav M., Parker, Roy, Puig, Sergi
Other Authors:	Agencia Estatal de Investigación (España)
Format:	artículo biblioteca
Language:	English
Published:	Springer Nature 2024-04-11
Subjects:	Eukaryotic Initiation Factor-2, Metabolism, Humans, Iron, Deficiencies, Mammals, Phosphorylation, Protein Biosynthesis, Saccharomyces cerevisiae, protein synthesis, iron, mineral deficiencies,
Online Access:	http://hdl.handle.net/10261/354199 http://dx.doi.org/10.13039/501100011033 https://api.elsevier.com/content/abstract/scopus_id/85189978486
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