Probable cytosolic iron-sulfur protein assembly protein CIAO1

CIAO1 (Probable cytosolic iron-sulfur protein assembly protein) is a key component of the cytosolic iron-sulfur protein assembly (CIA) complex, which mediates the incorporation of iron-sulfur clusters into extramitochondrial Fe/S proteins (UniProt: O76071). The protein interacts with CIAO2A, CIAO2B, and MMS19 to facilitate assembly of cytosolic-nuclear Fe/S proteins and maturation of specific iron-sulfur enzymes such as ACO1 and IREB2. CIAO1 additionally modulates WT1 transactivation activity and participates in the mitotic spindle-associated MMXD complex for chromosome segregation.

CIAO1 is associated with Multiple mitochondrial dysfunctions syndrome 10 (MMDS10; MIM 620960), an autosomal recessive disorder featuring muscle weakness, learning difficulties, and brain iron deposition (UniProt: O76071). Its role in iron-sulfur cluster assembly links it to cellular redox homeostasis and mitochondrial function.

In Alzheimer's disease, CIAO1 is downregulated in post-mortem AD brain tissue compared to age-matched controls, with a mean log2 fold-change of −0.27 (Chaparral AD proteomics). This reduction may impact iron-sulfur protein biogenesis and cellular iron metabolism in AD pathology.