Complexes of the Outer Mitochondrial Membrane Protein MitoNEET with Resveratrol-3-Sulfate

Title

Complexes of the Outer Mitochondrial Membrane Protein MitoNEET with Resveratrol-3-Sulfate

Creator

Arif W; Xu S; Isailovic D; Geldenhuys W J; Carroll R T; Funk M O

Publisher

Biochemistry

Date

2011
2011-06

Description

Binding of the thiazolidinedione antidiabetic drug pioglitazone led to the discovery of a novel outer mitochondrial membrane protein of unknown function called mitoNEET. The protein is homodimeric and contains a uniquely ligated two iron-two sulfur cluster in each of its two cytosolic domains. Electrospray ionization mass spectrometry was employed to characterize solutions of the soluble cytosolic domain (amino acids 32-108) of the protein. Ions characteristic of dimers containing the cofactors were readily detected under native conditions. mitoNEET responded to exposure to solutions at low pH by dissociation to give monomers that retained the cofactor, followed by dissociation of the cofactor in a concerted fashion. mitoNEET formed complexes with resveratrol-3-sulfate, one of the primary metabolites of the natural product resveratrol. Resveratrol itself showed no tendency to interact with mitoNEET. The formation of complexes was evident in both electrospray ionization mass spectrometry and isothermal titration calorimetry measurements. Up to eight molecules of the compound associated with the dimeric form of the protein in a sequential fashion. Dissociation constants determined by micorcalorimetry were in the range 5-16 mu M for the various binding sites. The only other known naturally occurring binding partner for mitoNEET at present is NADPH. It is very interesting that the iron-sulfur cluster containing protein interacts with two potentially redox active substances at the surface of mitochondria. These findings provide a new direction for research into two poorly understood, yet biomedically relevant, species.

Subject

activators; binding; Biochemistry & Molecular Biology; cluster; crystal-structure; grapes; identification; iron-sulfur proteins; life-span; mass-spectrometry; thiazolidinedione

Identifier

Format

Journal Article or Conference Abstract Publication

Search for Full-text

Users with a NEOMED Library login can search for full-text journal articles at the following url: https://libraryguides.neomed.edu/home

Rights

Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).

Pages

5806-5811

Issue

25

Volume

50

Citation

Arif W; Xu S; Isailovic D; Geldenhuys W J; Carroll R T; Funk M O, “Complexes of the Outer Mitochondrial Membrane Protein MitoNEET with Resveratrol-3-Sulfate,” NEOMED Bibliography Database, accessed June 25, 2021, https://neomed.omeka.net/items/show/8505.

Social Bookmarking