Identification of small molecules that bind to the mitochondrial protein mitoNEET.
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.
Department of Pharmaceutical Sciences, School of Pharmacy, West Virginia University, 1 Medical Center Drive, Morgantown, WV 26506, USA. Electronic address: werner.geldenhuys@hsc.wvu.edu.
Werner J
WJ
Geldenhuys
Spinal Cord and Brain Injury Research Center, University of Kentucky, Lexington, KY 40536, USA; Anatomy and Neurobiology, University of Kentucky, Lexington, KY 40536, USA.
Heather M
HM
Yonutas
Department of Chemistry and Biochemistry, University of Akron, Akron, OH 44325, USA.
Daniel L
DL
Morris
Spinal Cord and Brain Injury Research Center, University of Kentucky, Lexington, KY 40536, USA; Anatomy and Neurobiology, University of Kentucky, Lexington, KY 40536, USA.
Patrick G
PG
Sullivan
Department of Pharmaceutical Sciences, Northeast Ohio Medical University, Rootstown, OH 44240, USA.
Altaf S
AS
Darvesh
Department of Chemistry and Biochemistry, University of Akron, Akron, OH 44325, USA.
Thomas C
TC
Leeper
D007004:Hypoglycemic Agents / Q000737:chemistry / Q000378:metabolism; D008024:Ligands; D024101:Mitochondrial Proteins / Q000378:metabolism*; D011485:Protein Binding; D054852:Small Molecule Libraries; D045162:Thiazolidinediones / Q000737:chemistry / Q000378:metabolism
C525595:CISD1 protein, human; D007004:Hypoglycemic Agents; D008024:Ligands; D024101:Mitochondrial Proteins; D054852:Small Molecule Libraries; D045162:Thiazolidinediones
Bioenergetics; Glitazones; Mitochondria; Type II diabetes
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