Reduced Nicotinamide Adenine Dinucleotide Phosphate (NADPH) Blocks Transfer of [2Fe-2S] Clusters from MitoNEET to an Apo-Acceptor Protein

Abstract

MitoNEET is the founding member of the recently discovered CDGSH family of [2Fe-2S] proteins. Its structure contains a unique homodimeric fold with each monomer containing one [2Fe-2S] cluster (1). MitoNEET is a target of the thiazolidinedione (TZD) class of anti-diabetes drugs (2). Recently, it was reported that the [2Fe-2S] cluster in mitoNEET is destabilized upon binding of NADPH/NADP+ (3). As mitoNEET is capable of transferring its [2Fe-2S] clusters to an apo-acceptor protein (4) and an obvious question to ask is whether NADPH binding accelerates or abrogates cluster transfer. We show that NADPH blocks transfer of mitoNEET's [2Fe-2S] cluster to an apo-acceptor protein (see Figure). This suggests a likely functional role for the mitoNEET:NADPH/NADP+ interaction.(1) Paddock ML et al. (2007) PNAS 104 14342-7(2) Colca JR et al. (2004) Am J Physiol Endocrinol Metab 286 E252-60(3) Zhou et al. (2010) Biochemistry 49 9604-12(4) Zuris JA et al. (2011) PNAS 108 13047-52∗Supported by the Heme and Blood Proteins Training Grant 5T32DK007233-34View Large Image | View Hi-Res Image | Download PowerPoint Slide