Glutathione participates in the modulation of starvation-induced autophagy in carcinoma cells

Enrico Desideri, Giuseppe Filomeni, Maria Rosa Ciriolo

Research output: Contribution to journalArticlepeer-review

Abstract

Glutathione (γ-L-glutamyl-L-cysteinyl-glycine, GSH ) is the most abundant low molecular weight, thiol-containing compound within the cells and has a primary role in the antioxidant defense and intracellular signaling. Here we demonstrated that nutrient deprivation led to a significant decrease of intracellular GSH levels in three different carcinoma cell lines. This phenomenon was dependent on ABCC 1-mediated GSH extrusion, along with GCL inhibition and, to a minor extent, the formation of GSH -protein mixed disulfides that synergistically contributed to the modulation of autophagy by shifting the intracellular redox state toward more oxidizing conditions. Modulation of intracellular GSH by inhibiting its de novo synthesis through incubation with buthionine sulfoximine, or by maintaining its levels through GSH ethyl ester, affected the oxidation of protein thiols, such as PRDXs and consequently the kinetics of autophagy activation. We also demonstrated that thiol-oxidizing or -alkylating agents, such as diamide and diethyl maleate activated autophagy, corroborating the evidence that changes in thiol redox state contributed to the occurrence of autophagy.

Original languageEnglish
Pages (from-to)1769-1781
Number of pages13
JournalAutophagy
Volume8
Issue number12
DOIs
Publication statusPublished - Dec 2012

Keywords

  • ABCC1
  • BECN1
  • Diamide
  • Diethylmaleate
  • Glutathione
  • Peroxiredoxins
  • Redox state

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

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