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 journalArticlepeer-review

22 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 languageEnglish
Pages (from-to)5350-5353
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume26
Issue number21
DOIs
StatePublished - 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

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