Mitochondrial NEET protein (NEET protein)

Mitochondrial NEET proteins are a small, recently characterized family of iron–sulfur proteins comprising mitoNEET (CISD1), NAF-1 (CISD2), and MiNT (CISD3). They are integral to mitochondrial outer and inner membranes (and, in NAF-1’s case, also to the endoplasmic reticulum), where they regulate iron and reactive oxygen species homeostasis, control redox-sensitive signaling via their [2Fe–2S] clusters, and participate in electron transfer and metabolic homeostasis. NEET proteins are implicated in mitochondrial morphodynamics—including fission and fusion—by influencing membrane dynamics and inter-organelle contact sites. Dysfunction or altered expression of these proteins is associated with cancer, diabetes, neurodegenerative and inflammatory diseases, and several metabolic pathologies. MitoNEET is a direct target of the anti-diabetic drug pioglitazone, and experimental compounds (e.g., Mito-C) modulate their cluster transfer activities and mitochondrial dynamics.

Other names

mitoNEETNAF-1MiNTMiner1Miner2CDGSH iron-sulfur domain proteinsCISD1–3

Modulation of [2Fe–2S] cluster transfer (inhibition or stabilization). Alteration of mitochondrial morphology and ER-mitochondrial contacts. Regulation of iron and ROS levels. Inhibition of electron transfer (e.g., by drugs or nitric oxide).