ArticleThe Journal of cell biology2017
Multi-omics analysis identifies ATF4 as a key regulator of the mitochondrial stress response in mammals.
Article in The Journal of cell biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 530 papers.
What it found
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Who cites it
530 citing papers in PubMed, 818 citations in OpenAlex.
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- Pathogenic variants of the mitochondrial copper chaperones SCO1 and SCO2 reshape their respective interactomes and disrupt cellular phospholipid metabolism.bioRxiv : the preprint server for biology · 2026Article
- Peroxisomal Import Stress Drives Cellular Senescence through SCAF1-dependent Suppression of Mitoribosome Biogenesis.bioRxiv : the preprint server for biology · 2026Article
- Functional impact of Nth like DNA glycosylase 1 on mitochondrial dynamics.Nucleic acids research · 2026Article
- The role of ATF4 in neurons under mitochondrial stress.NAR genomics and bioinformatics · 2026Article
- Proteostasis of organelles in aging and disease.The FEBS journal · 2026Review
- ER proteostasis meets mitochondrial function: contact sites as hubs of communication and therapeutic targets.The FEBS journal · 2026Review
- Adaptation of OXPHOS biogenesis to cellular requirements.Protein science : a publication of the Protein Society · 2026Review
- A multilayered stress-response circuit: The mammalian mitochondrial UPR.The FEBS journal · 2026Review
- hY3 RNA binds and inhibits ribosomes and modulates the starvation-induced integrated stress response.Nucleic acids research · 2026Article
- Mitochondria as integrative regulators of ferroptosis in the female reproductive system.Biology of reproduction · 2026Review
- Transcriptomic analysis of mitohormesis associated with lifespan extension in Caenorhabditis elegans.GeroScience · 2026Article
- Mitochondrial quality control in health and disease: mechanisms and therapeutic targets.Signal transduction and targeted therapy · 2026Review
- Ribosome biogenesis and selective translational control as oncogenic vulnerabilities in hematologic malignancies.Molecular cancer · 2026Review
- Spatial ecology of breast cancer reveals co-evolution of proliferative and dormant niches.Genome medicine · 2026Article
- Reductive death is averted by a conserved de novo lipogenic switch.Molecular cell · 2026Article
- Multiple mechanisms lead to loss-of-function effects of pathogenic SARS2 variants.Disease models & mechanisms · 2026Article
470 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
Mitochondrial stress activates a mitonuclear response to safeguard and repair mitochondrial function and to adapt cellular metabolism to stress. Using a multiomics approach in mammalian cells treated with four types of mitochondrial stressors, we identify activating transcription factor 4 (ATF4) as the main regulator of the stress response. Surprisingly, canonical mitochondrial unfolded protein response genes mediated by ATF5 are not activated. Instead, ATF4 activates the expression of cytoprotective genes, which reprogram cellular metabolism through activation of the integrated stress response (ISR). Mitochondrial stress promotes a local proteostatic response by reducing mitochondrial ribosomal proteins, inhibiting mitochondrial translation, and coupling the activation of the ISR with the attenuation of mitochondrial function. Through a trans-expression quantitative trait locus analysis, we provide genetic evidence supporting a role for Fh1 in the control of Atf4 expression in mammals. Using gene expression data from mice and humans with mitochondrial diseases, we show that the ATF4 pathway is activated in vivo upon mitochondrial stress. Our data illustrate the value of a multiomics approach to characterize complex cellular networks and provide a versatile resource to identify new regulators of mitochondrial-related diseases.
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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.