ArticleMolecular cell2024
The HRI branch of the integrated stress response selectively triggers mitophagy.
Article in Molecular cell, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
What it found
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Who cites it
36 citing papers in PubMed, 49 citations in OpenAlex.
- Tryptoline stereoprobe elaboration identifies inhibitors of the GRPEL1-HSPA9 complex.Nature chemical biology · 2026Article
- 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
- Multiple mechanisms lead to loss-of-function effects of pathogenic SARS2 variants.Disease models & mechanisms · 2026Article
- Leucyl tRNA synthetase ameliorates cholestatic liver injury by inhibiting integrated stress response in mice.Scientific reports · 2026Article
- Structural insights into HRI kinase activity and inhibition.Biochemical Society transactions · 2026Review
- Pathogenic variants in the autophagy-tethering factor EPG5 drive neurodegeneration through mitochondrial dysfunction and innate immune activation.Nature communications · 2026Article
- Exercise-induced modulation of the unfolded protein response: a therapeutic avenue for muscle wasting disorders.Journal of physiology and biochemistry · 2026Review
- Quality control of protein import into mammalian mitochondria.Protein science : a publication of the Protein Society · 2026Review
- ATF4: Orchestrating Cellular Stress Adaptation, Metabolism, and Immune Regulation in Health and Disease.International journal of molecular sciences · 2026Review
- The integrated stress response suppresses PINK1-dependent mitophagy by preserving mitochondrial import efficiency.Nature communications · 2026Article
- Crosstalk between mitophagy and breast cancer: mechanisms of action and clinical applications.Journal of cancer research and clinical oncology · 2026Review
- Circular RNAs in metabolic health: bridging the gap between molecular biology and therapy.Cell death & disease · 2026Review
- The integrated stress response in apicomplexan and trypanosomatid parasites: balancing survival and pathogenesis.Frontiers in immunology · 2026Review
- The exercise-microbiota-queuine-tRNA axis in Parkinson's disease: evidence, uncertainties, and experimental priorities.Frontiers in neuroscience · 2026Review
- Dual relevance ofFrontiers in oncology · 2026Article
- MPC1 promotes the damage of human coronary endothelial cells in macrolide-resistant mycoplasma pneumoniae via inhibiting mitophagy.Frontiers in pediatrics · 2026Article
- The Role of Mitochondrial Quality Control in Manganese-induced Neurotoxicity.Neurotoxicity research · 2025Review
- Review
- Drug repurposing screen identifies an HRI activating compound that promotes adaptive mitochondrial remodeling in MFN2-deficient cells.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
To maintain mitochondrial homeostasis, damaged or excessive mitochondria are culled in coordination with the physiological state of the cell. The integrated stress response (ISR) is a signaling network that recognizes diverse cellular stresses, including mitochondrial dysfunction. Because the four ISR branches converge to common outputs, it is unclear whether mitochondrial stress detected by this network can regulate mitophagy, the autophagic degradation of mitochondria. Using a whole-genome screen, we show that the heme-regulated inhibitor (HRI) branch of the ISR selectively induces mitophagy. Activation of the HRI branch results in mitochondrial localization of phosphorylated eukaryotic initiation factor 2, which we show is sufficient to induce mitophagy. The HRI mitophagy pathway operates in parallel with the mitophagy pathway controlled by the Parkinson's disease related genes PINK1 and PARKIN and is mechanistically distinct. Therefore, HRI repurposes machinery that is normally used for translational initiation to trigger mitophagy in response to mitochondrial damage.
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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.