ArticlePLoS genetics2012
Protective coupling of mitochondrial function and protein synthesis via the eIF2α kinase GCN-2.
Article in PLoS genetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 203 papers.
What it found
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Who cites it
203 citing papers in PubMed, 318 citations in OpenAlex.
- Dichloroacetate Improves Animal Survival, Growth, Neuromuscular Activity, Mitochondrial Stress and Physiology, and Elevated Lactate in C. elegans pdha-1 and dld-1 RNAi Models of Pyruvate Dehydrogenase Complex Deficiency (PDCD).Journal of inherited metabolic disease · 2026Article
- Divergent Retrograde Signaling Pathways Coordinate Longevity and Metformin Responses in Complex I and Complex IV DeficientbioRxiv : the preprint server for biology · 2026Article
- A multilayered stress-response circuit: The mammalian mitochondrial UPR.The FEBS journal · 2026Review
- Depletion of TECPR2 leads to mitochondrial failure associated with neurodegeneration.Autophagy · 2026Article
- The mitochondrial unfolded protein response in human microglia disrupts neuronal-glial communication and promotes senescence.Nature neuroscience · 2026Article
- Mitochondrial quality control in health and disease: mechanisms and therapeutic targets.Signal transduction and targeted therapy · 2026Review
- Oxidative Stress and Diminished Mitochondrial Proteostatic Reserve Are Linked to Enhanced mtUPR Initiation in Aged Mouse Muscle.Aging cell · 2026Article
- Unfolding Resilience: Molecular Integration of the Integrated Stress Response and Mitochondrial UPR in Skeletal Muscle Homeostasis.Muscles (Basel, Switzerland) · 2026Review
- RNA binding proteinScience advances · 2026Article
- Mitochondrial unfolded protein response as a central stress-integration hub: mechanisms and implications in disease contexts.Burns & trauma · 2026Review
- Sirt1 coordinates the mitochondrial UPR and myocellular proteostasis to preserve muscle integrity during muscle atrophy in zebrafish.Frontiers in cell and developmental biology · 2026Article
- The GCN-2/eIF-2α/ATF-4 signaling pathway is involved inVirulence · 2025Article
- Translational regulation in stress biology.Nature cell biology · 2025Review
- Biological and clinical implications of a model of surveillance immunity.The Journal of clinical investigation · 2025Review
- Unveiling the intercompartmental signaling axis: Mitochondrial to ER Stress Response (MERSR) and its impact on proteostasis.PLoS genetics · 2025Article
- Differential impacts of ribosomal protein haploinsufficiency on mitochondrial function.The Journal of cell biology · 2025Article
- The integrated stress response in neurodegenerative diseases.Molecular neurodegeneration · 2025Review
- Unzipping the defense: a comprehensive review on bZIP transcription factors inFrontiers in cellular and infection microbiology · 2025Review
- The translation initiation factor eIF2α regulates lipid homeostasis and metabolic aging.Aging cell · 2025Article
- Stress response regulation of mRNA translation: Implications for antioxidant enzyme expression in cancer.Proceedings of the National Academy of Sciences of the United States of America · 2024Review
143 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Cells respond to defects in mitochondrial function by activating signaling pathways that restore homeostasis. The mitochondrial peptide exporter HAF-1 and the bZip transcription factor ATFS-1 represent one stress response pathway that regulates the transcription of mitochondrial chaperone genes during mitochondrial dysfunction. Here, we report that GCN-2, an eIF2α kinase that modulates cytosolic protein synthesis, functions in a complementary pathway to that of HAF-1 and ATFS-1. During mitochondrial dysfunction, GCN-2-dependent eIF2α phosphorylation is required for development as well as the lifespan extension observed in Caenorhabditis elegans. Reactive oxygen species (ROS) generated from dysfunctional mitochondria are required for GCN-2-dependent eIF2α phosphorylation but not ATFS-1 activation. Simultaneous deletion of ATFS-1 and GCN-2 compounds the developmental defects associated with mitochondrial stress, while stressed animals lacking GCN-2 display a greater dependence on ATFS-1 and stronger induction of mitochondrial chaperone genes. These findings are consistent with translational control and stress-dependent chaperone induction acting in complementary arms of the UPR(mt).
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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.