Binding of thiazolidinediones to the endoplasmic reticulum protein nutrient-deprivation autophagy factor-1.

Werner J Geldenhuys, Robert Skolik, Mary E Konkle, Michael A Menze, Timothy E Long, Aaron R Robart

Bioorganic & medicinal chemistry letters 2019 Apr 01

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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. Copyright © 2019. Published by Elsevier Ltd.

Citation

Werner J Geldenhuys, Robert Skolik, Mary E Konkle, Michael A Menze, Timothy E Long, Aaron R Robart. Binding of thiazolidinediones to the endoplasmic reticulum protein nutrient-deprivation autophagy factor-1. Bioorganic & medicinal chemistry letters. 2019 Apr 01;29(7):901-904