ArticleMolecular cell2023
A mitochondrial iron-responsive pathway regulated by DELE1.
Article in Molecular cell, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed, 72 citations in OpenAlex.
- Regulation of cellular proteostasis via mitochondrial protein import.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2026Review
- Mitochondrial depolarization stabilizes the vitamin BProceedings of the National Academy of Sciences of the United States of America · 2026Article
- 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
- Depletion of TECPR2 leads to mitochondrial failure associated with neurodegeneration.Autophagy · 2026Article
- Mitochondria-ER contacts function as an iron supply hub.Nature cell biology · 2026Article
- A transport-independent role for SLC25A12 in mitochondrial stress signalling.Nature cell biology · 2026Article
- Structural insights into HRI kinase activity and inhibition.Biochemical Society transactions · 2026Review
- Unfolding Resilience: Molecular Integration of the Integrated Stress Response and Mitochondrial UPR in Skeletal Muscle Homeostasis.Muscles (Basel, Switzerland) · 2026Review
- Targeting prohibitins activates the ISR through DELE1-HRI by impairing protein import into the mitochondrial matrix.Cell death and differentiation · 2026Article
- Proteolytic control of mitochondrial protein translocases.Protein science : a publication of the Protein Society · 2026Review
- Quality control of protein import into mammalian mitochondria.Protein science : a publication of the Protein Society · 2026Review
- The integrated stress response suppresses PINK1-dependent mitophagy by preserving mitochondrial import efficiency.Nature communications · 2026Article
- Function and regulation of the mitochondrial stress response.Nature structural & molecular biology · 2026Review
- Mutant CHCHD10 disrupts cytochrome c oxidation and activates mitochondrial retrograde signaling.EMBO molecular medicine · 2026Article
- Role of LONP1 in human diseases: molecular mechanisms and therapeutic potential.Cellular & molecular biology letters · 2026Review
- Targeting Infected Host Cell Heme Metabolism to Kill Malaria Parasites.Pharmaceuticals (Basel, Switzerland) · 2026Article
- The role of mitochondrial proteases in inflammation and immunity.Frontiers in immunology · 2026Review
- Mitochondrial protein import stress in Parkinson's disease: the TOM/TIM-PINK1/Parkin-DELE1/HRI axis linking mitochondrial proteostasis to neuronal death.Frontiers in cell and developmental biology · 2026Review
- Mitochondrial depolarization stabilizes the vitamin B12 chaperone MMADHC in the cytosol to increase MTR activity.bioRxiv : the preprint server for biology · 2025Article
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
The heme-regulated kinase HRI is activated under heme/iron deficient conditions; however, the underlying molecular mechanism is incompletely understood. Here, we show that iron-deficiency-induced HRI activation requires the mitochondrial protein DELE1. Notably, mitochondrial import of DELE1 and its subsequent protein stability are regulated by iron availability. Under steady-state conditions, DELE1 is degraded by the mitochondrial matrix-resident protease LONP1 soon after mitochondrial import. Upon iron chelation, DELE1 import is arrested, thereby stabilizing DELE1 on the mitochondrial surface to activate the HRI-mediated integrated stress response (ISR). Ablation of this DELE1-HRI-ISR pathway in an erythroid cell model enhances cell death under iron-limited conditions, suggesting a cell-protective role for this pathway in iron-demanding cell lineages. Our findings highlight mitochondrial import regulation of DELE1 as the core component of a previously unrecognized mitochondrial iron responsive pathway that elicits stress signaling following perturbation of iron homeostasis.
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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.