ArticleThe Journal of biological chemistry
The eIF2α kinase HRI triggers the autophagic clearance of cytosolic protein aggregates.
Article in The Journal of biological chemistry. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 38 citations in OpenAlex.
- Regulatory mechanism of heme-regulated inhibitor through autophosphorylation-driven activation and heme-induced deactivation.Journal of biochemistry · 2026Article
- Structural insights into HRI kinase activity and inhibition.Biochemical Society transactions · 2026Review
- Disruption of tRNA threonylation triggers RIG-I mediated anti-tumour immune response.Nature communications · 2026Article
- Integrated Stress Response Signatures Drive Monocyte Dysfunction in GBA1- and LRRK2-Linked Parkinson's Disease.Research square · 2026Article
- Integrated Stress Response Signatures Drive Monocyte Dysfunction inmedRxiv : the preprint server for health sciences · 2025Article
- Structural insights into allosteric inhibition of HRI kinase by heme binding via HDX-MS.The Biochemical journal · 2025Article
- Modulation of CREB3L2-ATF4 heterodimerization via proteasome inhibition and HRI activation in Alzheimer's disease pathology.Cell death & disease · 2025Article
- The Spectrum of Small Heat Shock Protein B8 (International journal of molecular sciences · 2025Review
- The integrated stress response in neurodegenerative diseases.Molecular neurodegeneration · 2025Review
- ROCK1 promotes B cell differentiation and proteostasis under stress through the heme-regulated proteins, BACH2 and HRI.JCI insight · 2025Article
- Cytosolic retention of HtrA2 during mitochondrial protein import stress triggers the DELE1-HRI pathway.Communications biology · 2024Article
- ATF4 Signaling in HIV-1 Infection: Viral Subversion of a Stress Response Transcription Factor.Biology · 2024Review
- Cellular Stress Responses against Coronavirus Infection: A Means of the Innate Antiviral Defense.Journal of microbiology and biotechnology · 2024Review
- Emerging role of microglia in inter-cellular transmission of α-synuclein in Parkinson's disease.Frontiers in aging neuroscience · 2024Review
- HSPB8 frameshift mutant aggregates weaken chaperone-assisted selective autophagy in neuromyopathies.Autophagy · 2023Article
- Article
- The integrated stress response in cancer progression: a force for plasticity and resistance.Frontiers in oncology · 2023Review
- A little less aggregation a little more replication: Viral manipulation of stress granules.Wiley interdisciplinary reviews. RNA · 2023Review
- Signaling plasticity in the integrated stress response.Frontiers in cell and developmental biology · 2023Review
- Review
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Authors and funding
13 authors at 5 institutions in 2 countries.
Funding
Abstract
Large cytosolic protein aggregates are removed by two main cellular processes, autophagy and the ubiquitin-proteasome system, and defective clearance of these protein aggregates results in proteotoxicity and cell death. Recently, we found that the eIF2α kinase heme-regulated inhibitory (HRI) induced a cytosolic unfolded protein response to prevent aggregation of innate immune signalosomes, but whether HRI acts as a general sensor of proteotoxicity in the cytosol remains unclear. Here we show that HRI controls autophagy to clear cytosolic protein aggregates when the ubiquitin-proteasome system is inhibited. We further report that silencing the expression of HRI resulted in decreased levels of BAG3 and HSPB8, two proteins involved in chaperone-assisted selective autophagy, suggesting that HRI may control proteostasis in the cytosol at least in part through chaperone-assisted selective autophagy. Moreover, knocking down the expression of HRI resulted in cytotoxic accumulation of overexpressed α-synuclein, a protein known to aggregate in Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy. In agreement with these data, protein aggregate accumulation and microglia activation were observed in the spinal cord white matter of 7-month-old Hri
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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.