ArticleeLife2019
HRI coordinates translation necessary for protein homeostasis and mitochondrial function in erythropoiesis.
Article in eLife, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
45 citing papers in PubMed, 63 citations in OpenAlex.
- From Cellular Stress to Systemic Adaptation: The Circadian Clock and Stress Response at Cellular and Systemic Levels.International journal of molecular sciences · 2026Review
- A multilayered stress-response circuit: The mammalian mitochondrial UPR.The FEBS journal · 2026Review
- Overcoming immunotherapy resistance in breast cancer: a novel strategy by targeting the integrated stress response.Frontiers in cell and developmental biology · 2026Review
- The ribosomal landscape in influenza A virus infection: from molecular mechanisms to clinical relevance.European respiratory review : an official journal of the European Respiratory Society · 2026Review
- HRI protein kinase in cytoplasmic heme sensing and mitochondrial stress response: Relevance to hematological and mitochondrial diseases.The Journal of biological chemistry · 2025Review
- Ribosomal protein deficiencies linked to Diamond-Blackfan anemia induce distinctive alterations of ATF4 expression.iScience · 2025Article
- Pulling back the mitochondria's iron curtain.npj metabolic health and disease · 2025Review
- The Integrated Stress Response in Pancreatic Development, Tissue Homeostasis, and Cancer.Gastroenterology · 2024Review
- Unraveling the roles and mechanisms of mitochondrial translation in normal and malignant hematopoiesis.Journal of hematology & oncology · 2024Review
- Myeloid PTEN loss affects the therapeutic response by promoting stress granule assembly and impairing phagocytosis by macrophages in breast cancer.Cell death discovery · 2024Article
- Sublethal engagement of apoptotic pathways in residual cancer.Trends in cell biology · 2024Review
- Computational identification of potential modulators of heme-regulated inhibitor (HRI) for pharmacological intervention against sickle cell disease.Research square · 2023Article
- FAM210A regulates mitochondrial translation and maintains cardiac mitochondrial homeostasis.Cardiovascular research · 2023Article
- Iron drives anabolic metabolism through active histone demethylation and mTORC1.Nature cell biology · 2023Article
- Surviving and Adapting to Stress: Translational Control and the Integrated Stress Response.Antioxidants & redox signaling · 2023Review
- TMEM11 regulates cardiomyocyte proliferation and cardiac repair via METTL1-mediated mCell death and differentiation · 2023Article
- Arginine metabolism regulates human erythroid differentiation through hypusination of eIF5A.Blood · 2023Article
- Iron-loaded deferiprone can support full hemoglobinization of cultured red blood cells.Scientific reports · 2023Article
- Iron Uptake ControlsAntioxidants (Basel, Switzerland) · 2023Article
- Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Iron and heme play central roles in the production of red blood cells, but the underlying mechanisms remain incompletely understood. Heme-regulated eIF2α kinase (HRI) controls translation by phosphorylating eIF2α. Here, we investigate the global impact of iron, heme, and HRI on protein translation in vivo in murine primary erythroblasts using ribosome profiling. We validate the known role of HRI-mediated translational stimulation of integratedstressresponse mRNAs during iron deficiency in vivo. Moreover, we find that the translation of mRNAs encoding cytosolic and mitochondrial ribosomal proteins is substantially repressed by HRI during iron deficiency, causing a decrease in cytosolic and mitochondrial protein synthesis. The absence of HRI during iron deficiency elicits a prominent cytoplasmic unfolded protein response and impairs mitochondrial respiration. Importantly, ATF4 target genes are activated during iron deficiency to maintain mitochondrial function and to enable erythroid differentiation. We further identify GRB10 as a previously unappreciated regulator of terminal erythropoiesis.
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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.