Glutaredoxin 2 prevents H2O2-induced cell apoptosis by protecting complex I activity in the mitochondria

Hongli Wu, Kuiyi Xing, Marjorie F. Lou

Research output: Contribution to journalArticle

48 Scopus citations

Abstract

Glutaredoxin 2 (Grx2) belongs to the oxidoreductase family and is an isozyme of glutaredoxin 1 (Grx1) present in the mitochondria, however its function is not well understood. The purpose of this study is to evaluate the potential anti-apoptotic function of Grx2 by examining its ability to protect complex I in the mitochondrial electron transport system using human lens epithelial cells as a model. We found that cells treated with 200μM hydrogen peroxide (H2O2) for 24h exhibited decreased viability and became apoptotic with corresponding Bax up-regulation, Bcl-2 down-regulation, caspase 3 activation and mitochondrial cytochrome c leakage. Grx2 over-expression (OE) could protect cells against H2O2-induced damage while Grx2 knockdown (KD) showed the opposite effect. Under the same conditions, H2O2 treatment caused 50% inactivation of complex I activity in control cells (vector only), 75% in Grx2 KD cells but only 20% in Grx2 OE cells. Furthermore, the inactivated complex I in the H2O2-treated cells could be protected mostly by importing the purified nascent Grx2 protein, but not the Grx2 protein mutated at the active site with C70S, or C73S, or with C70S plus C73S. Immunoprecipitation study also revealed that Grx2 co-precipitated with complex I, but not complex II, in the mitochondrial lysate. Thus, the mechanism of Grx2 protection against H2O2-induced apoptosis is likely associated with its ability to preserve complex I.

Original languageEnglish
Pages (from-to)1705-1715
Number of pages11
JournalBiochimica et Biophysica Acta - Bioenergetics
Volume1797
Issue number10
DOIs
StatePublished - Oct 2010

Keywords

  • Apoptosis
  • Complex I
  • Free radical
  • Glutaredoxin2
  • Hydrogen peroxide
  • Mitochondria
  • Reactive oxygen species (ROS)

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