ArticleNature communications2024
Specific activation of the integrated stress response uncovers regulation of central carbon metabolism and lipid droplet biogenesis.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed.
- Sprint interval exercise disrupts mitochondrial ultrastructure driving a unique mitochondrial stress response and remodelling in men.Nature communications · 2025Trial
- Coordinated regulation of the metaboproteome by Hsp90 chaperones controls metabolic plasticity.iScience · 2026Article
- Temporal gating dictates stress-induced transcript export from the nucleus.Genes & development · 2026Article
- Mitokines as bioenergetic stress signals in cardiovascular disease: mitochondrial communication, endocrine adaptation, and translational implications.Journal of bioenergetics and biomembranes · 2026Review
- Transcriptomic Reprogramming of the Human Placenta Following Maternal Opioid Exposure: Identification of Altered Metabolic and Translational Pathways.Current issues in molecular biology · 2026Article
- Mechanisms and therapeutic opportunities of the ribotoxic stress response in cancer.Molecular oncology · 2026Review
- The mitochondrial unfolded protein response in human microglia disrupts neuronal-glial communication and promotes senescence.Nature neuroscience · 2026Article
- Integrated Transcriptomic Analysis Identifies Potential Biomarkers in Castration-Resistant Prostate Cancer.World journal of oncology · 2026Article
- A membrane homeostatic response to lipid overload coordinates fatty acid metabolism.bioRxiv : the preprint server for biology · 2026Article
- Inhibition of the mitochondrial pyruvate carrier attenuates the integrated stress response activation in a cellular model of Huntington's disease.Molecular and cellular biochemistry · 2026Article
- A transport-independent role for SLC25A12 in mitochondrial stress signalling.Nature cell biology · 2026Article
- Allosteric disordering of eIF2B regulates the integrated stress response.Nature chemical biology · 2026Article
- Transcription Factor ATF4 Deletion Reprograms Glucose Metabolism in Clear Cell Renal Cell Carcinoma.Cancers · 2026Article
- The integrated developmental stress response (ISR-DASR) shift reveals a functional transition from cellular to stem cell organismal adaptation.Scientific reports · 2026Article
- Genomic insights into the tunicamycin-induced endoplasmic reticulum stress response in peripheral blood mononuclear cells: A comprehensive RNA sequencing analysis.Biochemistry and biophysics reports · 2026Article
- Mapping the GDF15 arm of the integrated stress response in human cells and tissues.Communications biology · 2026Article
- Host mature tRNAome as a decoding switch regulates antiviral and proviral responses.Nature communications · 2026Article
- Butyrate-producing gut bacteria restrain PBAT microplastic-triggered brain microglial lipotoxicity via a microbiota-butyrate-mTORC1-ISR relay along the gut-brain axis.Journal of neuroinflammation · 2026Article
- A molecular stabiliser of an inhibitory eIF2B-eIF2(αP) complex activates the Integrated Stress Response.Nature communications · 2026Article
- Temporal gating dictates stress-induced transcript export from the nucleus.bioRxiv : the preprint server for biology · 2026Article
Corrections and comments
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Authors and funding
12 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The integrated stress response (ISR) enables cells to cope with a variety of insults, but its specific contribution to downstream cellular outputs remains unclear. Using a synthetic tool, we selectively activate the ISR without co-activation of parallel pathways and define the resulting cellular state with multi-omics profiling. We identify time- and dose-dependent gene expression modules, with ATF4 driving only a small but sensitive subgroup that includes amino acid metabolic enzymes. This ATF4 response affects cellular bioenergetics, rerouting carbon utilization towards amino acid production and away from the tricarboxylic acid cycle and fatty acid synthesis. We also find an ATF4-independent reorganization of the lipidome that promotes DGAT-dependent triglyceride synthesis and accumulation of lipid droplets. While DGAT1 is the main driver of lipid droplet biogenesis, DGAT2 plays an essential role in buffering stress and maintaining cell survival. Together, we demonstrate the sufficiency of the ISR in promoting a previously unappreciated metabolic state.
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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.