Identification of small molecules that bind to the mitochondrial protein mitoNEET

Bioorg Med Chem Lett. 2016 Nov 1;26(21):5350-5353. doi: 10.1016/j.bmcl.2016.09.009. Epub 2016 Sep 6.


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.

Keywords: Bioenergetics; Glitazones; Mitochondria; Type II diabetes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Hypoglycemic Agents / chemistry
  • Hypoglycemic Agents / metabolism
  • Ligands
  • Mitochondrial Proteins / metabolism*
  • Protein Binding
  • Small Molecule Libraries*
  • Thiazolidinediones / chemistry
  • Thiazolidinediones / metabolism


  • CISD1 protein, human
  • Hypoglycemic Agents
  • Ligands
  • Mitochondrial Proteins
  • Small Molecule Libraries
  • Thiazolidinediones