ArticleCell death & disease2018
Inhibition of the ER stress IRE1α inflammatory pathway protects against cell death in mitochondrial complex I mutant cells.
Article in Cell death & disease, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
16 citing papers in PubMed, 25 citations in OpenAlex.
- Intestinal NSD2 Aggravates Nonalcoholic Steatohepatitis Through Histone Modifications.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Navigating the landscape of mitochondrial-ER communication in health and disease.Frontiers in molecular biosciences · 2024Review
- Tetracyclines activate mitoribosome quality control and reduce ER stress to promote cell survival.EMBO reports · 2023Article
- Glucocorticoid-mediated induction of ZBTB16 affects insulin secretion in human islets and EndoC-βH1 β-cells.iScience · 2023Article
- Circulating cell-free mtDNA release is associated with the activation of cGAS-STING pathway and inflammation in mitochondrial diseases.Journal of neurology · 2022Article
- Multi-OMICS study of a CHCHD10 variant causing ALS demonstrates metabolic rewiring and activation of endoplasmic reticulum and mitochondrial unfolded protein responses.Human molecular genetics · 2021Article
- Diversity and versatility of p38 kinase signalling in health and disease.Nature reviews. Molecular cell biology · 2021Review
- RNA-seq Characterization of Melanoma Phenotype Switch in 3D Collagen after p38 MAPK Inhibitor Treatment.Biomolecules · 2021Article
- Tetracyclines promote survival and fitness in mitochondrial disease models.Nature metabolism · 2021Article
- A Colon-Targeted Prodrug, 4-Phenylbutyric Acid-Glutamic Acid Conjugate, Ameliorates 2,4-Dinitrobenzenesulfonic Acid-Induced Colitis in Rats.Pharmaceutics · 2020Article
- UPR modulation of host immunity by Pseudomonas aeruginosa in cystic fibrosis.Clinical science (London, England : 1979) · 2020Article
- Protein Palmitoylation Regulates Cell Survival by Modulating XBP1 Activity in Glioblastoma Multiforme.Molecular therapy oncolytics · 2020Article
- TMEM173 Drives Lethal Coagulation in Sepsis.Cell host & microbe · 2020Article
- Review
- The Reciprocal Causation of the ASK1-JNK1/2 Pathway and Endoplasmic Reticulum Stress in Diabetes-Induced Cognitive Decline.Frontiers in cell and developmental biology · 2020Article
- Theaflavins attenuate ethanol‑induced oxidative stress and cell apoptosis in gastric mucosa epithelial cells via downregulation of the mitogen‑activated protein kinase pathway.Molecular medicine reports · 2018Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Mitochondrial mutations cause bioenergetic defects associated with failures to use the electron transfer chain and oxidize substrates. These defects are exacerbated under energetic stress conditions and ultimately cause cell deterioration and death. However, little is known about cellular strategies that rescue mitochondrial stress failures and maintain cell survival under these conditions. Here, we have designed and performed a high-throughput chemical screen to identify small molecules that rescue human mitochondrial complex I mutations from energetic stress-induced cell death. The top positive hits were a series of sulfonylureas that efficiently maintain prolonged cell survival and growth under energetic stress conditions. The addition of galactose instead of glucose, to experimentally force mitochondrial respiration, triggered an initial ER stress response that was associated with IRE1α-dependent inflammatory signals including JNK and p38 MAP kinases in mutant cells. Sulfonylureas, similar to inhibition of IRE1α and p38 MAP kinase, potently blocked this ER stress inflammatory and cell death pathway and maintained viability and cell growth under severe energetic stress conditions. These studies reveal that sulfonylureas and specific inhibition of the IRE1α inflammatory pathway protect against cell death and can be used to rescue bioenergetic failures in mitochondrial complex I-mutated cells under stress conditions.
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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.