ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2012
Glutathione-dependent reductive stress triggers mitochondrial oxidation and cytotoxicity.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 107 papers.
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Who cites it
107 citing papers in PubMed, 192 citations in OpenAlex.
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- Curcumin and ferulic acid activate PPARγ-PGC1α signaling and improve mitochondrial function in a 6-OHDA-induced Parkinson's cellular model.Scientific reports · 2026Article
- UVA Irradiation Promotes ROS-Mediated Formation of the Common Deletion in Mitochondrial DNA.Life (Basel, Switzerland) · 2026Article
- Neutrophil redox imbalance in acute coronary syndrome.Journal of medical biochemistry · 2026Article
- Reductive stress in cancer immunology and targeted therapy.Acta biochimica et biophysica Sinica · 2026Review
- Identifying mitochondrial genes and potential biological functions in pre-eclampsia: bioinformatics and experimental insights.Frontiers in genetics · 2026Article
- Beyond Radical Scavengers: Focus on NADPH Oxidases (NOX) Inhibitors as New Agents for Antioxidant Therapy in Alzheimer's Disease.Antioxidants (Basel, Switzerland) · 2025Review
- Reductive stress: The key pathway in metabolic disorders induced by overnutrition.Journal of advanced research · 2025Review
- The Mechanism of Fraxetin as a Sustainable Fungicide for Larch Shoot Blight: Lipid Peroxidation and Oxidative Stress inJournal of fungi (Basel, Switzerland) · 2025Article
- Impaired Renal Function Due to Reductive Stress Is Associated with Excessive Consumption ofAntioxidants (Basel, Switzerland) · 2025Article
- Review
- Combating Reactive Oxygen Species (ROS) with Antioxidant Supramolecular Polymers.ACS applied materials & interfaces · 2025Article
- Nanozyme-driven multifunctional dressings: moving beyond enzyme-like catalysis in chronic wound treatment.Military Medical Research · 2025Review
- Redox Imbalance in Inflammation: The Interplay of Oxidative and Reductive Stress.Antioxidants (Basel, Switzerland) · 2025Review
- Does the Type of Semen Affect the Phosphoproteome of Turkey (International journal of molecular sciences · 2025Article
- Ferroptosis and Alzheimer's: unveiling new avenues for the treatment and prevention.Metabolic brain disease · 2025Review
- The Role of Reductive Stress in the Pathogenesis of Endocrine-Related Metabolic Diseases and Cancer.International journal of molecular sciences · 2025Review
- The implication of aberrant NRF2 activation in management of female cancers.Frontiers in oncology · 2025Review
47 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
To investigate the effects of the predominant nonprotein thiol, glutathione (GSH), on redox homeostasis, we employed complementary pharmacological and genetic strategies to determine the consequences of both loss- and gain-of-function GSH content in vitro. We monitored the redox events in the cytosol and mitochondria using reduction-oxidation sensitive green fluorescent protein (roGFP) probes and the level of reduced/oxidized thioredoxins (Trxs). Either H(2)O(2) or the Trx reductase inhibitor 1-chloro-2,4-dinitrobenzene (DNCB), in embryonic rat heart (H9c2) cells, evoked 8 or 50 mV more oxidizing glutathione redox potential, E(hc) (GSSG/2GSH), respectively. In contrast, N-acetyl-L-cysteine (NAC) treatment in H9c2 cells, or overexpression of either the glutamate cysteine ligase (GCL) catalytic subunit (GCLC) or GCL modifier subunit (GCLM) in human embryonic kidney 293 T (HEK293T) cells, led to 3- to 4-fold increase of GSH and caused 7 or 12 mV more reducing E(hc), respectively. This condition paradoxically increased the level of mitochondrial oxidation, as demonstrated by redox shifts in mitochondrial roGFP and Trx2. Lastly, either NAC treatment (EC(50) 4 mM) or either GCLC or GCLM overexpression exhibited increased cytotoxicity and the susceptibility to the more reducing milieu was achieved at decreased levels of ROS. Taken together, our findings reveal a novel mechanism by which GSH-dependent reductive stress triggers mitochondrial oxidation and cytotoxicity.
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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.