Protein S-glutathionylation confers cellular resistance to ferroptosis induced by glutathione depletion
Ju Y., Zhang Y., Tian X., Zhu N., Zheng Y., Qiao Y.
Animal Study, published in Redox Biol (2025) — summary generated from the PubMed abstract.
Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.
- Level A · Stronger Clinical Evidence
- Level B · Emerging clinical evidence with positive signals
- Level C · Early human research exploring benefits
- Level D · Scientific groundwork from lab and animal studies
- Emerging · Emerging topic under active research
This page is generated from the PubMed record. The Thai description is an automated summary of bibliographic fields and the abstract, not a full translation, and is not medical advice.
- Study type
- Animal Study
- Journal
- Redox Biol (2025)
- Reported sample size
- —
- Source database
- Europe PMC
- PMID
- 40354766
- PMCID
- PMC12139022
- DOI
- 10.1016/j.redox.2025.103660
- Citations
- 12
Abstract (original English)
Ferroptosis is one of the most critical biological consequences of glutathione depletion. Excessive oxidative stress, indicated by an elevated oxidized glutathione (GSSG)/reduced glutathione (GSH) ratio, is recognized as a key driver of ferroptosis. However, in glutathione depletion-induced ferroptosis, a marked decrease in total glutathione levels (including both GSH and GSSG) is frequently observed, yet its significance remains understudied. Protein S-glutathionylation (protein-SSG) levels are closely linked to the redox state and cellular glutathione pools including GSH and GSSG. To date, the role of protein-SSG during cell ferroptosis induced by glutathione depletion remains poorly understood. Here, we demonstrated that upregulation of CHAC1, a glutathione-degrading enzyme, acted as a key regulator of protein-SSG formation and exacerbated glutathione depletion-induced ferroptosis. This effect was observed in both in vitro and in vivo models, including erastin-induced ferroptosis across multiple cell lines and acetaminophen overdose-triggered ferroptosis in hepatocytes. Deficiency of CHAC1 resulted in increased glutathione pools, enhanced protein-SSG, improved liver function, and attenuation of hepatocyte ferroptosis upon acetaminophen challenge. These protective effects were reversed by CHAC1 overexpression. Using quantitative redox proteomics, we identified glutathione poo
What this study does not prove
- • This study does not prove SVF is an approved treatment or a replacement for standard care.
- • This is preclinical work; animal or laboratory results cannot be applied to humans.
Evidence level
Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.
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