Binding of thiazolidinediones to the endoplasmic reticulum protein nutrient-deprivation autophagy factor-1 |
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| Authors: | Werner J. Geldenhuys Robert Skolik Mary E. Konkle Michael A. Menze Timothy E. Long Aaron R. Robart |
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| Affiliation: | 1. Department of Pharmaceutical Sciences, School of Pharmacy, West Virginia University, Morgantown, WV 26506, United States;2. Department of Neuroscience, School of Medicine, West Virginia University, Morgantown, WV 26506, United States;3. Department of Chemistry, Ball State University, Muncie, IN 47306, United States;4. Department of Biology, University of Louisville, Louisville, KY 40229, United States;5. Department of Pharmaceutical Sciences, School of Pharmacy, Marshall University, Huntington, WV, United States;6. Department of Biochemistry, School of Medicine, West Virginia University, Morgantown, WV 26506, United States |
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| Abstract: | Nutrient-deprivation autophagy factor-1 (NAF-1, miner1; gene cisd2) is part of the [2Fe-2S]-containing protein family which includes mitoNEET (gene cisd1) and MiNT (miner2; gene cisd3). These proteins are redox active and are thought to play an important role in cellular energy homeostasis with NAF-1 playing a critical role in calcium regulation and aging. To date, no studies have investigated potential ligand interaction with NAF-1. Here we show that the thiazolidinediones pioglitazone and rosiglitazone along with the mitoNEET ligand, NL-1, bind to NAF-1 with low micromolar affinities. Further, we show that overexpression of NAF-1 in hepatocellular carcinoma (HepG2) cells reduces inhibition of mitochondrial respiration by pioglitazone. Our findings support the need for further efforts of the rational design of selective NAF-1 ligands. |
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| Keywords: | Glitazones Wolfram syndrome CDGSH Zinc-finger CISD' miner1 |
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