The CDGSH Iron Sulfur Domain 1 (CISD1), also known as mitoNEET, is a protein that plays a crucial role in cellular iron metabolism and mitochondrial function. This protein is characterized by the presence of a CDGSH iron-sulfur binding domain, which is essential for its function.
The CDGSH domain is a unique iron-sulfur binding motif that coordinates a [2Fe-2S] cluster. The domain is defined by the consensus sequence [C-X-C-X2-(S/T)-X3-P-X-C-D-G-(S/A/T)-H], where the CDGSH sequence is underlined, and the 3Cys-1His 2Fe-2S coordinating amino acids are indicated in bold . This domain was initially thought to be a zinc finger binding domain but was later shown to bind a 2Fe-2S iron-sulfur cluster .
CISD1 is an integral membrane protein located in the outer mitochondrial membrane. It functions as a homodimer and is involved in the regulation of iron and reactive oxygen metabolism . The protein is implicated in various physiological processes, including diabetes, obesity, cancer, cardiovascular disease, and neurodegeneration .
The CDGSH domain is ancient in origin and appears in many important plant and animal proteins. It is believed to have appeared early in evolution, possibly linked to the heavy use of iron-sulfur driven metabolism by early organisms . The human CISD1 protein is thought to have originated from a mitochondrial endosymbiotic event .
CISD1, along with other CDGSH proteins, plays a significant role in maintaining cellular iron homeostasis and protecting cells from oxidative stress. The protein’s ability to bind and transport iron is crucial for the function of several mitochondrial enzymes . Dysregulation of CISD1 has been associated with various diseases, including diabetes, cancer, and neurodegenerative disorders .
Research on CISD1 has provided valuable insights into its structure, function, and evolutionary history. The protein’s role in disease mechanisms makes it a potential target for therapeutic interventions. Recombinant forms of CISD1 are used in research to study its function and to develop potential treatments for diseases associated with iron metabolism and mitochondrial dysfunction .