ArticleCell death and differentiation2019
Loss of glutathione redox homeostasis impairs proteostasis by inhibiting autophagy-dependent protein degradation.
Article in Cell death and differentiation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 43 citations in OpenAlex.
- Loss of PIK3CA AllowsCells · 2026Article
- Loss of PIK3CA allowsbioRxiv : the preprint server for biology · 2026Article
- The transsulfuration pathway suppresses the embryonic lethal phenotype of glutathione reductase mutants in Caenorhabditis elegans.G3 (Bethesda, Md.) · 2025Article
- Review
- TRP14 is the rate-limiting enzyme for intracellular cystine reduction and regulates proteome cysteinylation.The EMBO journal · 2024Article
- Thioredoxin (Trx): A redox target and modulator of cellular senescence and aging-related diseases.Redox biology · 2024Review
- Mitochondrial Glutathione in Cellular Redox Homeostasis and Disease Manifestation.International journal of molecular sciences · 2024Review
- Article
- A Diet Containing Rutin Ameliorates Brain Intracellular Redox Homeostasis in a Mouse Model of Alzheimer's Disease.International journal of molecular sciences · 2023Article
- Circulating (Poly)phenol Metabolites: Neuroprotection in a 3D Cell Model of Parkinson's Disease.Molecular nutrition & food research · 2022Article
- Cobalt chloride has beneficial effects across species through a hormetic mechanism.Frontiers in cell and developmental biology · 2022Article
- Global transcriptome profiling reveals genes responding to overproduction of a small secretory, a high cysteine- and a high glycosylation-bearing protein inBiotechnology reports (Amsterdam, Netherlands) · 2021Article
- Cholesterol alters mitophagy by impairing optineurin recruitment and lysosomal clearance in Alzheimer's disease.Molecular neurodegeneration · 2021Article
- A conserved cysteine-based redox mechanism sustains TFEB/HLH-30 activity under persistent stress.The EMBO journal · 2021Article
- Synergistic activation of AMPK prevents from polyglutamine-induced toxicity in Caenorhabditis elegans.Pharmacological research · 2020Article
- S-adenosylmethionine: A metabolite critical to the regulation of autophagy.Cell proliferation · 2020Review
- Reactive Species in Huntington Disease: Are They Really the Radicals You Want to Catch?Antioxidants (Basel, Switzerland) · 2020Review
- Cross-talk between redox signalling and protein aggregation.Biochemical Society transactions · 2020Review
- Pathological Roles of Mitochondrial Oxidative Stress and Mitochondrial Dynamics in Cardiac Microvascular Ischemia/Reperfusion Injury.Biomolecules · 2020Review
- Emerging Evidence Highlighting the Importance of Redox Dysregulation in the Pathogenesis of Amyotrophic Lateral Sclerosis (ALS).Frontiers in cellular neuroscience · 2020Article
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Authors and funding
19 authors at 9 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In the presence of aggregation-prone proteins, the cytosol and endoplasmic reticulum (ER) undergo a dramatic shift in their respective redox status, with the cytosol becoming more oxidized and the ER more reducing. However, whether and how changes in the cellular redox status may affect protein aggregation is unknown. Here, we show that C. elegans loss-of-function mutants for the glutathione reductase gsr-1 gene enhance the deleterious phenotypes of heterologous human, as well as endogenous worm aggregation-prone proteins. These effects are phenocopied by the GSH-depleting agent diethyl maleate. Additionally, gsr-1 mutants abolish the nuclear translocation of HLH-30/TFEB transcription factor, a key inducer of autophagy, and strongly impair the degradation of the autophagy substrate p62/SQST-1::GFP, revealing glutathione reductase may have a role in the clearance of protein aggregates by autophagy. Blocking autophagy in gsr-1 worms expressing aggregation-prone proteins results in strong synthetic developmental phenotypes and lethality, supporting the physiological importance of glutathione reductase in the regulation of misfolded protein clearance. Furthermore, impairing redox homeostasis in both yeast and mammalian cells induces toxicity phenotypes associated with protein aggregation. Together, our data reveal that glutathione redox homeostasis may be central to proteostasis maintenance through autophagy regulation.
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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 Socratic graph.