Cytosolic Iron-Sulfur Assembly Component 3 (CIAO3)

CIAO3 is a 53 kDa protein that functions as a component of the cytosolic iron-sulfur protein assembly (CIA) complex, which catalyzes incorporation of iron-sulfur clusters into extramitochondrial Fe/S proteins (UniProt: Q9H6Q4). The protein also appears to negatively regulate hypoxia-inducible factor 1-alpha (HIF1A) expression, though this effect may be indirect.

CIAO3 is involved in cellular iron-sulfur cluster homeostasis and biogenesis, processes essential for the function of numerous metabolic enzymes and electron-transport proteins across diverse cellular compartments.

In Alzheimer's disease, CIAO3 is significantly downregulated in post-mortem AD brain tissue compared to age-matched controls, with a mean log2 fold-change of −0.67 (Chaparral AD proteomics). This reduction was observed via TMT-labeled proteomics across multiple subcellular fractions from human brain tissue. The downregulation may reflect impaired iron-sulfur cluster biogenesis or altered cellular iron metabolism in AD pathology.