CDGSH iron–sulfur domain-containing protein 1 (mitoNEET)

**CDGSH iron–sulfur domain-containing protein 1 (mitoNEET)** is a homodimeric iron–sulfur cluster protein located on the outer mitochondrial membrane and serves as a founding member of the CISD protein family[1][5]. Each subunit harbors a [2Fe–2S] cluster coordinated by three cysteines and one histidine in a unique “CCCH-type” motif[1][3]. Functionally, mitoNEET acts as a redox-sensitive regulator of mitochondrial metabolism and is involved in electron transfer processes, as well as potentially transferring its Fe–S cluster to acceptor proteins in the cytosol, thereby influencing iron homeostasis[4][7]. Originally identified as a binding site for the antidiabetic drug pioglitazone, mitoNEET has since emerged as a potential therapeutic target in type 2 diabetes, obesity, cancer, and neurodegenerative diseases[4][6][7]. Crystal structures and biochemical studies support a role in redox signaling, iron-sulfur cluster trafficking, and metabolic regulation. Drugs like pioglitazone bind to mitoNEET and modulate its redox state and enzymatic activity, linking its function to metabolic and disease processes[4][6]. Inhibiting or dysregulating mitoNEET’s function may carry risks related to mitochondrial impairment and disruption of iron metabolism[4][5].

Other names

mitoNEETCISD1CDGSH iron–sulfur domain-containing protein 1

Inhibition or modulation of electron transfer activity by binding to the [2Fe–2S] cluster (pioglitazone, NL-1) Stabilization or alteration of the Fe–S cluster redox potential (pioglitazone) Potential interference with FMNH2 binding and electron transfer (pioglitazone, NL-1)