CDGSH iron-sulfur domain-containing protein 1 (CISD1)

CDGSH iron-sulfur domain-containing protein 1 (CISD1, commonly known as mitoNEET) is an evolutionarily conserved, outer mitochondrial membrane protein characterized by a [2Fe-2S] iron-sulfur cluster coordinated in a 3Cys:1His motif within a CDGSH-type zinc finger domain[1][2][6]. It is involved in regulation of mitochondrial iron handling, redox homeostasis, oxidative phosphorylation, and acts as a redox and iron-sulfur cluster sensor, transferring clusters to other acceptor proteins as needed[2][4][5][6]. CISD1 modulates processes such as oxidative stress response, lipid peroxidation suppression (anti-ferroptosis), and overall mitochondrial function, with implications in metabolic diseases (such as diabetes and obesity), cancer biology, neurodegeneration, aging, and response to environmental oxidative stress[2][5][7]. Notable drugs that interact with mitoNEET include pioglitazone and rosiglitazone, which may partially mediate their anti-diabetic actions by modulating mitoNEET's mitochondrial regulatory roles[1][2][6]. Given its centrality in mitochondrial function, CISD1 is under consideration as a therapeutic target for diseases associated with mitochondrial dysfunction, though its essential role also signals possible safety and metabolic liability if directly targeted[2][3][7].

Other names

mitoNEETC10orf70ZCD1MDS029zinc finger CDGSH-type domain 1cysteine transaminase CISD1

Ligands (e.g., pioglitazone, rosiglitazone) can bind mitoNEET and modulate its function, impacting mitochondrial oxidative capacity, bioenergetics, and redox homeostasis[1][2][6]. Modulation of iron-sulfur cluster transfer and redox sensing, affecting downstream metabolic and stress response pathways[2][5][6].