Copper-induced cell death and the protective role of glutathione: The implication of impaired protein folding rather than oxidative stress
- Saporito Magriñá, Christian Martín
- Musacco Sebio, Rosario Natalia
- Andrieux, Geoffroy
- Kook, Lucas
- Orrego, Manuel Tomás
- Tuttolomondo, María Victoria
- Desimone, Martín Federico
- Boerries, Melanie
- Borner, Christoph
- Repetto, Marisa Gabriela
DOIAbstract
Copper (Cu) is a bioelement essential for a myriad of enzymatic reactions, which when present in high concentration leads to cytotoxicity. Whereas Cu toxicity is usually assumed to originate from the metal's ability to enhance lipid peroxidation, the role of oxidative stress has remained uncertain since no antioxidant therapy has ever been effective. Here we show that Cu overload induces cell death independently of the metal's ability to oxidize the intracellular milieu. In fact, cells neither lose control of their thiol homeostasis until briefly before the onset of cell death, nor trigger a consistent antioxidant response. As expected, glutathione (GSH) protects the cell from Cu-mediated cytotoxicity but, surprisingly, fully independent of...
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