ArticleeLife2020
Distinct mitochondrial defects trigger the integrated stress response depending on the metabolic state of the cell.
Article in eLife, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 158 papers, 2 of them syntheses that pooled it.
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Who cites it
158 citing papers in PubMed, 2 syntheses or guidelines pooled it, 244 citations in OpenAlex.
- A systematic review on the biochemical threshold of mitochondrial genetic variants.Genome research · 2024Pooled it
- Mechanisms of imipridones in targeting mitochondrial metabolism in cancer cells.Neuro-oncology · 2021Pooled it
- Circulating markers of NADH-reductive stress correlate with mitochondrial disease severity.The Journal of clinical investigation · 2021Trial
- Peroxisomal Import Stress Drives Cellular Senescence through SCAF1-dependent Suppression of Mitoribosome Biogenesis.bioRxiv : the preprint server for biology · 2026Article
- Mitochondrial depolarization stabilizes the vitamin BProceedings of the National Academy of Sciences of the United States of America · 2026Article
- Metabolites with a message: impacts on epigenetics and implications for epimetabopathies.EMBO reports · 2026Review
- The role of ATF4 in neurons under mitochondrial stress.NAR genomics and bioinformatics · 2026Article
- Mitochondrial profiling across macrophage states reveals inhibition of IL-4/IL-13 reprogramming by the integrated stress response.Science advances · 2026Article
- Spatial ecology of breast cancer reveals co-evolution of proliferative and dormant niches.Genome medicine · 2026Article
- Low-Temperature HILIC Provides Enhanced Separations and Stability for LC-MS-Based Metabolomics.Journal of proteome research · 2026Article
- Reductive death is averted by a conserved de novo lipogenic switch.Molecular cell · 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
- Molecular damage associated with ageing drives inflammation in cardiovascular disease.Nature reviews. Cardiology · 2026Review
- Mitochondrial integrated stress response activation creates a therapeutic vulnerability to MCL-1 inhibition in acute myeloid leukemia.Cell death & disease · 2026Article
- Copper transport to mitochondria by SLC25A3 contributes to skeletal myoblast differentiation and is required for survival of differentiated myotubes.bioRxiv : the preprint server for biology · 2026Article
- AMC-F1 regulates mitochondria-autophagy crosstalk independent of nutrient stress.Nature communications · 2026Article
- Succinate dehydrogenase loss suppresses pyrimidine biosynthesis via succinate-mediated inhibition of aspartate transcarbamylase.Nature metabolism · 2026Article
- Mapping the GDF15 arm of the integrated stress response in human cells and tissues.Communications biology · 2026Article
- Unfolding Resilience: Molecular Integration of the Integrated Stress Response and Mitochondrial UPR in Skeletal Muscle Homeostasis.Muscles (Basel, Switzerland) · 2026Review
- Mitochondria-targeted metformin analogs activate the ER stress-unfolded protein response pathway to drive apoptosis in pancreatic cancer.Cell death & disease · 2026Article
98 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Mitochondrial dysfunction is associated with activation of the integrated stress response (ISR) but the underlying triggers remain unclear. We systematically combined acute mitochondrial inhibitors with genetic tools for compartment-specific NADH oxidation to trace mechanisms linking different forms of mitochondrial dysfunction to the ISR in proliferating mouse myoblasts and in differentiated myotubes. In myoblasts, we find that impaired NADH oxidation upon electron transport chain (ETC) inhibition depletes asparagine, activating the ISR via the eIF2α kinase GCN2. In myotubes, however, impaired NADH oxidation following ETC inhibition neither depletes asparagine nor activates the ISR, reflecting an altered metabolic state. ATP synthase inhibition in myotubes triggers the ISR via a distinct mechanism related to mitochondrial inner-membrane hyperpolarization. Our work dispels the notion of a universal path linking mitochondrial dysfunction to the ISR, instead revealing multiple paths that depend both on the nature of the mitochondrial defect and on the metabolic state of the cell.
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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.