Identification of small molecules that bind to the mitochondrial protein mitoNEET

Werner J. Geldenhuys; Heather M. Yonutas; Daniel L. Morris; Patrick G. Sullivan; Altaf S. Darvesh; Thomas C. Leeper

doi:10.1016/j.bmcl.2016.09.009

Identification of small molecules that bind to the mitochondrial protein mitoNEET

Werner J. Geldenhuys, Heather M. Yonutas, Daniel L. Morris, Patrick G. Sullivan, Altaf S. Darvesh, Thomas C. Leeper

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

26 Scopus citations

Abstract

MitoNEET (CISD1) is a 2Fe-2S iron-sulfur cluster protein belonging to the zinc-finger protein family. Recently mitoNEET has been shown to be a major role player in the mitochondrial function associated with metabolic type diseases such as obesity and cancers. The anti-diabetic drug pioglitazone and rosiglitazone were the first identified ligands to mitoNEET. Since little is known about structural requirements for ligand binding to mitoNEET, we screened a small set of compounds to gain insight into these requirements. We found that the thiazolidinedione (TZD) warhead as seen in rosiglitazone was not an absolutely necessity for binding to mitoNEET. These results will aid in the development of novel compounds that can be used to treat mitochondrial dysfunction seen in several diseases.

Original language	English
Pages (from-to)	5350-5353
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	26
Issue number	21
DOIs	https://doi.org/10.1016/j.bmcl.2016.09.009
State	Published - 2016

Bibliographical note

Funding Information:
This work was funded in part by the Michael J. Fox Foundation for Parkinson’s Research to WJG. The project described was supported by the National Institute of General Medical Sciences , U54GM104942 . The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

Publisher Copyright:
© 2016

Keywords

Bioenergetics
Glitazones
Mitochondria
Type II diabetes

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

UN SDGs

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

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10.1016/j.bmcl.2016.09.009

Cite this

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title = "Identification of small molecules that bind to the mitochondrial protein mitoNEET",

abstract = "MitoNEET (CISD1) is a 2Fe-2S iron-sulfur cluster protein belonging to the zinc-finger protein family. Recently mitoNEET has been shown to be a major role player in the mitochondrial function associated with metabolic type diseases such as obesity and cancers. The anti-diabetic drug pioglitazone and rosiglitazone were the first identified ligands to mitoNEET. Since little is known about structural requirements for ligand binding to mitoNEET, we screened a small set of compounds to gain insight into these requirements. We found that the thiazolidinedione (TZD) warhead as seen in rosiglitazone was not an absolutely necessity for binding to mitoNEET. These results will aid in the development of novel compounds that can be used to treat mitochondrial dysfunction seen in several diseases.",

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note = "Funding Information: This work was funded in part by the Michael J. Fox Foundation for Parkinson{\textquoteright}s Research to WJG. The project described was supported by the National Institute of General Medical Sciences , U54GM104942 . The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Publisher Copyright: {\textcopyright} 2016",

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doi = "10.1016/j.bmcl.2016.09.009",

language = "English",

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AU - Yonutas, Heather M.

AU - Morris, Daniel L.

AU - Sullivan, Patrick G.

AU - Darvesh, Altaf S.

AU - Leeper, Thomas C.

N1 - Funding Information: This work was funded in part by the Michael J. Fox Foundation for Parkinson’s Research to WJG. The project described was supported by the National Institute of General Medical Sciences , U54GM104942 . The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Publisher Copyright: © 2016

PY - 2016

Y1 - 2016

N2 - MitoNEET (CISD1) is a 2Fe-2S iron-sulfur cluster protein belonging to the zinc-finger protein family. Recently mitoNEET has been shown to be a major role player in the mitochondrial function associated with metabolic type diseases such as obesity and cancers. The anti-diabetic drug pioglitazone and rosiglitazone were the first identified ligands to mitoNEET. Since little is known about structural requirements for ligand binding to mitoNEET, we screened a small set of compounds to gain insight into these requirements. We found that the thiazolidinedione (TZD) warhead as seen in rosiglitazone was not an absolutely necessity for binding to mitoNEET. These results will aid in the development of novel compounds that can be used to treat mitochondrial dysfunction seen in several diseases.

AB - MitoNEET (CISD1) is a 2Fe-2S iron-sulfur cluster protein belonging to the zinc-finger protein family. Recently mitoNEET has been shown to be a major role player in the mitochondrial function associated with metabolic type diseases such as obesity and cancers. The anti-diabetic drug pioglitazone and rosiglitazone were the first identified ligands to mitoNEET. Since little is known about structural requirements for ligand binding to mitoNEET, we screened a small set of compounds to gain insight into these requirements. We found that the thiazolidinedione (TZD) warhead as seen in rosiglitazone was not an absolutely necessity for binding to mitoNEET. These results will aid in the development of novel compounds that can be used to treat mitochondrial dysfunction seen in several diseases.

KW - Bioenergetics

KW - Glitazones

KW - Mitochondria

KW - Type II diabetes

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Identification of small molecules that bind to the mitochondrial protein mitoNEET

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

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