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

• Published in: Biochimica et biophysica acta 2010-10, Vol.1797 (10), p.1705-1715
• Main Authors: Wu, Hongli, Xing, Kuiyi, Lou, Marjorie F.
• Format: Article
• Language: English
• ISSN: 0005-2728; 0006-3002
• DOI: 10.1016/j.bbabio.2010.06.003

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 200 μM hydrogen peroxide (H 2 O 2 ) for 24 h 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 H 2 O 2 -induced damage while Grx2 knockdown (KD) showed the opposite effect. Under the same conditions, H 2 O 2 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. This antiapoptotic function of Grx2 is specific as rotenone, a complex I specific inhibitor, could block this Grx2-mediated protection of complex I activity. Immunoprecipitation study also revealed that Grx2 co-precipitated with complex I in the mitochondrial lysate. Thus, the mechanism of Grx2 protection against H 2 O 2 -induced apoptosis is likely associated with its ability to preserve complex I.