Binding of thiazolidinediones to the endoplasmic reticulum protein nutrient-deprivation autophagy factor-1. Issue 7 (1st April 2019)

• Record Type: Journal Article
• Authors: Geldenhuys, Werner J.; Skolik, Robert; Konkle, Mary E.; Menze, Michael A.; Long, Timothy E.; Robart, Aaron R.
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 29:Issue 7(2019)
• Page Start: 901
• Page End: 904
• Publication Date: 2019-04-01
• Subjects: Glitazones -- Wolfram syndrome -- CDGSH -- Zinc-finger -- CISD' miner1; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2019.01.041
• Languages: English
• ISSNs: 0960-894X

Abstract

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. Graphical abstract: