ArticleScience advances2021
Adaptation to mitochondrial stress requires CHOP-directed tuning of ISR.
Article in Science advances, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 92 papers.
What it found
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The trial behind it
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Who cites it
92 citing papers in PubMed, 133 citations in OpenAlex.
- Circulating factors induced by time-restricted eating drive metabolic reprogramming in endothelial cells.GeroScience · 2026Article
- Regulation of cellular proteostasis via mitochondrial protein import.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2026Review
- Mitokines as bioenergetic stress signals in cardiovascular disease: mitochondrial communication, endocrine adaptation, and translational implications.Journal of bioenergetics and biomembranes · 2026Review
- A multilayered stress-response circuit: The mammalian mitochondrial UPR.The FEBS journal · 2026Review
- Spatial architecture of immunometabolism: Mitochondrial‑organelle interfaces in immune signaling (Review).International journal of molecular medicine · 2026Review
- A transport-independent role for SLC25A12 in mitochondrial stress signalling.Nature cell biology · 2026Article
- AMC-F1 regulates mitochondria-autophagy crosstalk independent of nutrient stress.Nature communications · 2026Article
- Mapping the GDF15 arm of the integrated stress response in human cells and tissues.Communications biology · 2026Article
- The Integrated Stress Response Protein, eIF2α, Modulates UPRCardiovascular toxicology · 2026Article
- Metabolic and transcriptional plasticity supports CD8Immunity · 2026Article
- Pregnancy precipitates metabolic imbalance and accelerates death in an animal model of mitochondrial cardiomyopathy.Molecular metabolism · 2026Article
- Cell intrinsic versus cell extrinsic control of plasma cell longevity.Trends in immunology · 2026Review
- Deficient Cardiolipin Remodelling Alters Muscle Fibre Composition and Neuromuscular Connectivity in Barth Syndrome.Journal of cachexia, sarcopenia and muscle · 2026Article
- ATF4 Coordinates Transcriptomic and Structural Adaptations in Aging Muscle.bioRxiv : the preprint server for biology · 2026Article
- Activation of the protective arm of renin-angiotensin system enhances mitochondrial turnover improving respiration and decreasing integrated stress response in a human Complex III deficiency model.bioRxiv : the preprint server for biology · 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
- Mutant CHCHD10 disrupts cytochrome c oxidation and activates mitochondrial retrograde signaling.EMBO molecular medicine · 2026Article
- Polymer-specific nanoplastics trigger oxidative stress, inflammatory activation, and mitoepigenetic remodeling:Frontiers in toxicology · 2026Article
- The energy resistance principle.Cell metabolism · 2025Review
32 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 4 countries.
Funding
Abstract
In response to disturbed mitochondrial gene expression and protein synthesis, an adaptive transcriptional response sharing a signature of the integrated stress response (ISR) is activated. We report an intricate interplay between three transcription factors regulating the mitochondrial stress response: CHOP, C/EBPβ, and ATF4. We show that CHOP acts as a rheostat that attenuates prolonged ISR, prevents unfavorable metabolic alterations, and postpones the onset of mitochondrial cardiomyopathy. Upon mitochondrial dysfunction, CHOP interaction with C/EBPβ is needed to adjust ATF4 levels, thus preventing overactivation of the ATF4-regulated transcriptional program. Failure of this interaction switches ISR from an acute to a chronic state, leading to early respiratory chain deficiency, energy crisis, and premature death. Therefore, contrary to its previously proposed role as a transcriptional activator of mitochondrial unfolded protein response, our results highlight a role of CHOP in the fine-tuning of mitochondrial ISR in mammals.
Identifiers
What OpenQuestion holds
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.