CDGSH iron-sulfur domain-containing protein 3 (MiNT)

MiNT (Mitochondrial inner NEET protein), also known as CISD3, is a member of the NEET family of iron-sulfur proteins, which also includes mitoNEET (CISD1) and NAF-1 (CISD2) [2.1.1, 2.3.3]. Unlike its homodimeric counterparts, MiNT is a monomeric protein localized within the mitochondrial matrix and contains two distinct [2Fe-2S] clusters [2.1.1, 3.3.4]. It plays a vital role in cellular homeostasis by regulating mitochondrial iron levels and reactive oxygen species (ROS) through the transfer of iron-sulfur clusters to acceptor proteins like ferredoxins and respiratory complex I subunits [2.1.1, 3.2.1]. MiNT is frequently upregulated in various cancers, where it supports rapid tumor growth and provides resistance to ferroptosis, making it an attractive target for anticancer therapies [2.2.1, 3.2.3]. Additionally, it is implicated in metabolic diseases such as diabetes and neurodegenerative conditions like Parkinson's disease [2.2.1, 2.3.5]. Drugs such as thiazolidinediones (e.g., pioglitazone) and experimental ligands (e.g., NL-1) interact with MiNT by modulating the stability of its iron-sulfur clusters, thereby influencing mitochondrial bioenergetics and cell survival [2.2.2, 3.3.1].

Other names

CISD3Miner2Mitochondrial inner NEET proteinMitochondrial inner membrane NEET protein

Modulation of [2Fe-2S] cluster stability and transfer to acceptor proteins, regulating mitochondrial iron and ROS levels. In cancer, drugs destabilize the clusters to induce iron release and ROS-mediated cell death; in metabolic disease, ligands may stabilize the clusters to improve mitochondrial bioenergetics.