The Outer Mitochondrial Membrane Protein mitoNEET Contains a Novel Redox-active 2Fe-2S Cluster

The outer mitochondrial membrane protein mitoNEET was discovered as a binding target of pioglitazone, an insulin-sensitizing drug of the thiazolidinedione class used to treat type 2 diabetes (Colca, J. R., McDonald, W. G., Waldon, D. J., Leone, J. W., Lull, J. M., Bannow, C. A., Lund, E. T., and Mat...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of biological chemistry 2007-08, Vol.282 (33), p.23745-23749
Main Authors: Wiley, Sandra E., Paddock, Mark L., Abresch, Edward C., Gross, Larry, van der Geer, Peter, Nechushtai, Rachel, Murphy, Anne N., Jennings, Patricia A., Dixon, Jack E.
Format: Article
Language:English
Subjects:
Binding Sites
Cysteine
Histidine
Humans
Hydrogen-Ion Concentration
Iron-Binding Proteins - chemistry
Iron-Sulfur Proteins - chemistry
Membrane Proteins - chemistry
Mitochondrial Membranes - chemistry
Mitochondrial Proteins - chemistry
Oxidation-Reduction
Spectrum Analysis
Zinc Fingers
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The outer mitochondrial membrane protein mitoNEET was discovered as a binding target of pioglitazone, an insulin-sensitizing drug of the thiazolidinedione class used to treat type 2 diabetes (Colca, J. R., McDonald, W. G., Waldon, D. J., Leone, J. W., Lull, J. M., Bannow, C. A., Lund, E. T., and Mathews, W. R. (2004) Am. J. Physiol. 286, E252–E260). We have shown that mitoNEET is a member of a small family of proteins containing a 39-amino-acid CDGSH domain. Although the CDGSH domain is annotated as a zinc finger motif, mitoNEET was shown to contain iron (Wiley, S. E., Murphy, A. N., Ross, S. A., van der Geer, P., and Dixon, J. E. (2007) Proc. Natl. Acad. Sci. U. S. A. 104, 5318–5323). Optical and electron paramagnetic resonance spectroscopy showed that it contained a redox-active pH-labile Fe-S cluster. Mass spectrometry showed the loss of 2Fe and 2S upon cofactor extrusion. Spectroscopic studies of recombinant proteins showed that the 2Fe-2S cluster was coordinated by Cys-3 and His-1. The His ligand was shown to be involved in the observed pH lability of the cluster, indicating that loss of this ligand via protonation triggered release of the cluster. mitoNEET is the first identified 2Fe-2S-containing protein located in the outer mitochondrial membrane. Based on the biophysical data and domain fusion analysis, mitoNEET may function in Fe-S cluster shuttling and/or in redox reactions.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.C700107200