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Thiol‐based Antioxidants Trigger Transient Mitochondrial Oxidation
Author(s) -
Beaudoin Jessica Nicole,
Kolossov Vladimir L.,
Hanafin William,
DiLiberto Stephen,
Kenis P. G.,
Gaskins H. R.
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1011.14
Subject(s) - mitochondrion , cytosol , glutathione , reactive oxygen species , oxidative stress , chemistry , microbiology and biotechnology , respiratory chain , mitochondrial matrix , redox , biochemistry , antioxidant , cell , biophysics , biology , enzyme , organic chemistry
Perturbation of redox homeostasis has been associated with tumorigenisis, however, the underlying mechanisms are poorly understood due to analytical limitations. In this regard, we have used a ratiometric, redox‐sensitive green fluorescent protein attached to glutaredoxin to monitor real time redox potentials of the glutathione pool in the cytosol and mitochondrial matrix of colonic adenocarcinoma (HCT116), glioblastoma (GL261), and isogenic tumorigenic and normal porcine fibroblast (PF161) cell lines. Intriguingly, this wide array of cell types consistently exhibited mitochondrial oxidation following exposure to the antioxidants N‐acetylcysteine and glutathione ethyl ester. These chemotherapeutic drugs immediately triggered full oxidation of the mitochondrial sensor, followed by rapid recovery. This effect was observed exclusively in mitochondria, leading us to hypothesize involvement of the electron transport chain (ETC), the main source of reactive oxygen species. By systematically inhibiting respiratory complexes of the ETC, we identified complex III to be responsible for this short‐lived mitochondrial oxidation. The discovery that antioxidants initiate mitochondrial stress may provide insight into the efficacy of antioxidants in conjunction with chemotherapy. Our current focus is to determine if or how this mechanism may contribute to neoplastic transformation. Support granted by NIH R33 CA137719