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


Department of Pharmaceutical Sciences, School of Pharmacy, West Virginia University, Morgantown, WV 26506, United States; Department of Neuroscience, School of Medicine, West Virginia University, Morgantown, WV 26506, United States. Electronic address: [Email]


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.


CDGSH,CISD' miner1,Glitazones,Wolfram syndrome,Zinc-finger,

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