Redox Potential of the Outer-Mitochondrial Membrane 2Fe-2S Protein MitoNEET

Abstract

MitoNEET was recently discovered as a binding target for the anti-diabetes drug pioglitazone (1). It harbors a pH-labile 2Fe-2S cluster coordinated by three cysteines and one histidine (His87) (2). We measured a pH-dependent redox potential of +35 mV (pH 7.5) that lies intermediate between most low potential 4Cys-coordinated ferredoxin-like centers (∼-300 mV) and most high potential 2Cys-2His-coordinated Rieske centers (∼+300 mV) (3). In addition, its redox potential was ∼40mV lower in the presence of phosphate ions. This can be explained by binding of a phosphate ion near the cluster as reported elsewhere (Homer, poster). The H87C mutant, which becomes 4 Cys coordinated, has a more negative reduction potential similar to a ferredoxin (∼ -200mV). Our results show that the redox potential is sensitive to the coordination of the cluster and that mitoNEET's unique coordination geometry is likely essential for its unknown redox function. (1) Colca et al. (2004) Am J Physiol Endocrinol Metab 286 E252-E260. (2) Paddock et al. (2007) Proc Natl. Acad. Sci USA 104, 14342-14347. (3) Meyer (2008) J Biol Inorg Chem 13, 157-170 Supported by NIH (GM41637, GM54038 and DK54441).View Large Image Figure ViewerDownload Hi-res image Download (PPT) View Large Image Figure ViewerDownload Hi-res image Download (PPT)