MitoNEET is a uniquely folded 2Fe-2S outer mitochondrial membrane protein stabilized by pioglitazone

Mark L. Paddock; Sandra E. Wiley; Herbert L. Axelrod; Aina E. Cohen; Melinda Roy; Edward C. Abresch; Dominique Capraro; Anne N. Murphy; Rachel Nechushtai; Jack E. Dixon; Patricia A. Jennings

doi:10.1073/pnas.0707189104

MitoNEET is a uniquely folded 2Fe-2S outer mitochondrial membrane protein stabilized by pioglitazone

Mark L. Paddock, Sandra E. Wiley, Herbert L. Axelrod, Aina E. Cohen, Melinda Roy, Edward C. Abresch, Dominique Capraro, Anne N. Murphy, Rachel Nechushtai, Jack E. Dixon, Patricia A. Jennings^*

^*Corresponding author for this work

Department of Plant and Environmental Sciences (Natural Sciences)

Research output: Contribution to journal › Article › peer-review

232 Scopus citations

Abstract

Iron-sulfur (Fe-S) proteins are key players in vital processes involving energy homeostasis and metabolism from the simplest to most complex organisms. We report a 1.5 Å x-ray crystal structure of the first identified outer mitochondrial membrane Fe-S protein, mitoNEET. Two protomers intertwine to form a unique dimeric structure that constitutes a new fold to not only the ∼650 reported Fe-S protein structures but also to all known proteins. We name this motif the NEET fold. The protomers form a two-domain structure: a β-cap domain and a cluster-binding domain that coordinates two acid-labile 2Fe-2S clusters. Binding of pioglitazone, an insulin-sensitizing thiazolidinedione used in the treatment of type 2 diabetes, stabilizes the protein against 2Fe-2S cluster release. The biophysical properties of mitoNEET suggest that it may participate in a redox-sensitive signaling and/or in Fe-S cluster transfer.

Original language	English
Pages (from-to)	14342-14347
Number of pages	6
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	104
Issue number	36
DOIs	https://doi.org/10.1073/pnas.0707189104
State	Published - 4 Sep 2007

Keywords

Diabetes
FeS cluster
Iron homeostasis
Oxidative stress
Thiazolidinedione

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1073/pnas.0707189104

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Paddock, M. L., Wiley, S. E., Axelrod, H. L., Cohen, A. E., Roy, M., Abresch, E. C., Capraro, D., Murphy, A. N., Nechushtai, R., Dixon, J. E., & Jennings, P. A. (2007). MitoNEET is a uniquely folded 2Fe-2S outer mitochondrial membrane protein stabilized by pioglitazone. Proceedings of the National Academy of Sciences of the United States of America, 104(36), 14342-14347. https://doi.org/10.1073/pnas.0707189104

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abstract = "Iron-sulfur (Fe-S) proteins are key players in vital processes involving energy homeostasis and metabolism from the simplest to most complex organisms. We report a 1.5 {\AA} x-ray crystal structure of the first identified outer mitochondrial membrane Fe-S protein, mitoNEET. Two protomers intertwine to form a unique dimeric structure that constitutes a new fold to not only the ∼650 reported Fe-S protein structures but also to all known proteins. We name this motif the NEET fold. The protomers form a two-domain structure: a β-cap domain and a cluster-binding domain that coordinates two acid-labile 2Fe-2S clusters. Binding of pioglitazone, an insulin-sensitizing thiazolidinedione used in the treatment of type 2 diabetes, stabilizes the protein against 2Fe-2S cluster release. The biophysical properties of mitoNEET suggest that it may participate in a redox-sensitive signaling and/or in Fe-S cluster transfer.",

keywords = "Diabetes, FeS cluster, Iron homeostasis, Oxidative stress, Thiazolidinedione",

author = "Paddock, {Mark L.} and Wiley, {Sandra E.} and Axelrod, {Herbert L.} and Cohen, {Aina E.} and Melinda Roy and Abresch, {Edward C.} and Dominique Capraro and Murphy, {Anne N.} and Rachel Nechushtai and Dixon, {Jack E.} and Jennings, {Patricia A.}",

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Paddock, ML, Wiley, SE, Axelrod, HL, Cohen, AE, Roy, M, Abresch, EC, Capraro, D, Murphy, AN, Nechushtai, R, Dixon, JE & Jennings, PA 2007, 'MitoNEET is a uniquely folded 2Fe-2S outer mitochondrial membrane protein stabilized by pioglitazone', Proceedings of the National Academy of Sciences of the United States of America, vol. 104, no. 36, pp. 14342-14347. https://doi.org/10.1073/pnas.0707189104

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AU - Paddock, Mark L.

AU - Wiley, Sandra E.

AU - Axelrod, Herbert L.

AU - Cohen, Aina E.

AU - Roy, Melinda

AU - Abresch, Edward C.

AU - Capraro, Dominique

AU - Murphy, Anne N.

AU - Nechushtai, Rachel

AU - Dixon, Jack E.

AU - Jennings, Patricia A.

PY - 2007/9/4

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N2 - Iron-sulfur (Fe-S) proteins are key players in vital processes involving energy homeostasis and metabolism from the simplest to most complex organisms. We report a 1.5 Å x-ray crystal structure of the first identified outer mitochondrial membrane Fe-S protein, mitoNEET. Two protomers intertwine to form a unique dimeric structure that constitutes a new fold to not only the ∼650 reported Fe-S protein structures but also to all known proteins. We name this motif the NEET fold. The protomers form a two-domain structure: a β-cap domain and a cluster-binding domain that coordinates two acid-labile 2Fe-2S clusters. Binding of pioglitazone, an insulin-sensitizing thiazolidinedione used in the treatment of type 2 diabetes, stabilizes the protein against 2Fe-2S cluster release. The biophysical properties of mitoNEET suggest that it may participate in a redox-sensitive signaling and/or in Fe-S cluster transfer.

AB - Iron-sulfur (Fe-S) proteins are key players in vital processes involving energy homeostasis and metabolism from the simplest to most complex organisms. We report a 1.5 Å x-ray crystal structure of the first identified outer mitochondrial membrane Fe-S protein, mitoNEET. Two protomers intertwine to form a unique dimeric structure that constitutes a new fold to not only the ∼650 reported Fe-S protein structures but also to all known proteins. We name this motif the NEET fold. The protomers form a two-domain structure: a β-cap domain and a cluster-binding domain that coordinates two acid-labile 2Fe-2S clusters. Binding of pioglitazone, an insulin-sensitizing thiazolidinedione used in the treatment of type 2 diabetes, stabilizes the protein against 2Fe-2S cluster release. The biophysical properties of mitoNEET suggest that it may participate in a redox-sensitive signaling and/or in Fe-S cluster transfer.

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MitoNEET is a uniquely folded 2Fe-2S outer mitochondrial membrane protein stabilized by pioglitazone

Abstract

Keywords

UN SDGs

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