کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1907823 | 1534961 | 2015 | 9 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Reduction of mitochondrial protein mitoNEET [2Fe–2S] clusters by human glutathione reductase Reduction of mitochondrial protein mitoNEET [2Fe–2S] clusters by human glutathione reductase](/preview/png/1907823.png)
• MitoNEET [2Fe–2S] clusters are fully reduced in mouse heart cell extracts by NADPH.
• Human glutathione reductase can efficiently reduce mitoNEET [2Fe–2S] clusters.
• Reduced mitoNEET [2Fe–2S] clusters are reversibly oxidized by H2O2.
• MitoNEET may act as a novel redox sensor to regulate mitochondrial function.
The human mitochondrial outer membrane protein mitoNEET is a newly discovered target of the type 2 diabetes drug pioglitazone. Structurally, mitoNEET is a homodimer with each monomer containing an N-terminal transmembrane α helix tethered to the mitochondrial outer membrane and a C-terminal cytosolic domain hosting a redox-active [2Fe–2S] cluster. Genetic studies have shown that mitoNEET has a central role in regulating energy metabolism in mitochondria. However, the specific function of mitoNEET remains largely elusive. Here we find that the mitoNEET [2Fe–2S] clusters can be efficiently reduced by Escherichia coli thioredoxin reductase and glutathione reductase in an NADPH-dependent reaction. Purified human glutathione reductase has the same activity as E. coli thioredoxin reductase and glutathione reductase to reduce the mitoNEET [2Fe–2S] clusters. However, rat thioredoxin reductase, a human thioredoxin reductase homolog that contains selenocysteine in the catalytic center, has very little or no activity to reduce the mitoNEET [2Fe–2S] clusters. N-ethylmaleimide, a potent thiol modifier, completely inhibits human glutathione reductase from reducing the mitoNEET [2Fe–2S] clusters, indicating that the redox-active disulfide in the catalytic center of human glutathione reductase may be directly involved in reducing the mitoNEET [2Fe–2S] clusters. Additional studies reveal that the reduced mitoNEET [2Fe–2S] clusters in mouse heart cell extracts can be reversibly oxidized by hydrogen peroxide without disruption of the clusters, suggesting that the mitoNEET [2Fe–2S] clusters may undergo redox transition to regulate energy metabolism in mitochondria in response to oxidative signals.
Journal: Free Radical Biology and Medicine - Volume 81, April 2015, Pages 119–127