ArticleProceedings of the National Academy of Sciences of the United States of America2019
Iron regulatory protein 2 modulates the switch from aerobic glycolysis to oxidative phosphorylation in mouse embryonic fibroblasts.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 57 citations in OpenAlex.
- Iron, Copper, and Zinc Dyshomeostasis in Cardiovascular and Cerebrovascular Diseases: Redox Mechanisms, Evidence Levels, and Translational Prospects.International journal of molecular sciences · 2026Review
- Review
- Elevated lactate production exacerbates PM2.5-induced pulmonary fibrosis by stabilizing TGF-β1.Journal of advanced research · 2026Article
- HDAC3 Preserves the primordial follicle reserve by epigenetically suppressing ferroptosis in pregranulosa cells.Cellular and molecular life sciences : CMLS · 2026Article
- Iron Deficiency in Pulmonary Hypertension-Prevalence, Impact on Prognosis and Disease Burden in Pulmonary Arterial Hypertension and Pulmonary Hypertension Related to Hypoxia: A Review.International journal of molecular sciences · 2026Review
- IRP1 deficiency alters mitochondrial metabolism and protects against metabolic syndrome pathologies.JCI insight · 2026Article
- Targeting Iron Regulatory Protein 2 in Tumor-associated Macrophages Activates Antitumor Immunity in NSCLC via Modulating SphK1-PD-L1 Axis.International journal of biological sciences · 2026Article
- A novel strategy to target metabolic dependencies in acute myeloid leukemia.Cell death & disease · 2025Article
- Low Wall Shear Stress Promotes Atheroma via Arterial Iron Accumulation.Arteriosclerosis, thrombosis, and vascular biology · 2025Article
- Macrophages Internalize Epithelial-Derived Extracellular Vesicles That Contain Ferritin via the Macrophage Scavenger Receptor 1 to Promote Inflammatory Bowel Disease.Journal of extracellular vesicles · 2025Article
- Iron Replacement Attenuates Hypoxic Pulmonary Hypertension by Remodeling Energy Metabolism via Regulating the HIF2α/Mitochondrial Complex I, III/ROS Axis.Biomolecules · 2025Article
- Iron regulatory protein 1-deficient mice exhibit hypospermatogenesis.The Journal of biological chemistry · 2025Article
- Mammalian SLC39A13 promotes ER/Golgi iron transport and iron homeostasis in multiple compartments.Nature communications · 2024Article
- Novel biallelic variants in IREB2 cause an early-onset neurodegenerative disorder in a Chinese pedigree.Orphanet journal of rare diseases · 2024Article
- Interplay of FXN expression and lipolysis in white adipocytes plays a critical role in insulin sensitivity in Friedreich's ataxia mouse model.Scientific reports · 2024Article
- Downregulation of Iron-Sulfur Cluster Biogenesis May Contribute to Hyperglycemia-Mediated Diabetic Peripheral Neuropathy in Murine Models.Antioxidants (Basel, Switzerland) · 2024Article
- Inhibition of IRP2-dependent reprogramming of iron metabolism suppresses tumor growth in colorectal cancer.Cell communication and signaling : CCS · 2024Article
- Iron regulatory protein 2 contributes to antimicrobial immunity by preserving lysosomal function in macrophages.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Adipose knockout of H-ferritin improves energy metabolism in mice.Molecular metabolism · 2024Article
- Oxygen and Iron Availability Shapes Metabolic Adaptations of Cancer Cells.World journal of oncology · 2024Review
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The importance of the role of iron regulatory proteins (IRPs) in mitochondrial iron homeostasis and function has been raised. To understand how an IRP affects mitochondrial function, we used globally Irp2-depleted mouse embryonic fibroblasts (MEFs) and found that Irp2 ablation significantly induced the expression of both hypoxia-inducible factor subunits, Hif1α and Hif2α. The increase of Hif1α up-regulated its targeted genes, enhancing glycolysis, and the increase of Hif2α down-regulated the expression of iron-sulfur cluster (Fe-S) biogenesis-related and electron transport chain (ETC)-related genes, weakening mitochondrial respiration. Inhibition of Hif1α by genetic knockdown or a specific inhibitor prevented Hif1α-targeted gene expression, leading to decreased aerobic glycolysis. Inhibition of Hif2α by genetic knockdown or selective disruption of the heterodimerization of Hif2α and Hif1β restored the mitochondrial ETC and coupled oxidative phosphorylation (OXPHOS) by enhancing Fe-S biogenesis and increasing ETC-related gene expression. Our results indicate that Irp2 modulates the metabolic switch from aerobic glycolysis to OXPHOS that is mediated by Hif1α and Hif2α in MEFs.
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