The NFU1 gene encodes a mitochondrial matrix protein that is thought to be involved in iron-sulfur cluster assembly (1). Expression of Nfu1p is regulated by specific degradation of its mRNA in a process involving Tis11p, which binds to and mediates degradation of mRNAs encoding proteins involved in iron metabolism (3). The nfu1 single mutant does not exhibit large differences from wild type. Activity of aconitase (Aco1p), which is an iron-sulfur cluster-containing enzyme, is reduced in the nfu1 null mutant (1, 4), and mitochondrial iron accumulation is decreased (1). In vitro assembly of iron-sulfur clusters is 40% reduced in mitochondrial lysates from the nfu1 null mutant (2).

NFU1 exhibits genetic interactions with several genes involved in mitochondrial iron metabolism. It was first isolated via a synthetic lethal genetic interaction with SSQ1, which encodes a mitochondrial hsp70-type molecular chaperone that has also been implicated in iron-sulfur cluster assembly (1). The ISU1 gene encodes another mitochondrial protein involved in iron-sulfur cluster assembly; an isu1 single null mutant has no obvious phenotype, but the nfu1 isu1 double mutant exhibits temperature-sensitive fermentative growth and a decreased respiratory growth rate (1). Null nfu1 mutations also exhibit a synthetic slow growth phenotype when combined with null mutations in YFH1, which encodes the mitochondrial iron-storage protein frataxin (5).

Nfu1p is one of three S. cerevisiae proteins with similarity to the bacterial NifU protein, which has been well characterized in nitrogen-fixing bacteria and is thought to act as a scaffold for iron-sulfur cluster assembly (6). Nfu1p has similarity to the C terminus of NifU, while Isu1p and Isu2p have similarity to the NifU N terminus (1). NFU1 is conserved from bacteria to mammals, and the temperature sensitivity and respiratory defect of the isu1 nfu1 double mutant is functionally complemented by its Arabidopsis orthologs (7, 8). The putative mammalian ortholog of NFU1 is HIRIP5 (OMIM). HIRIP5 itself is not implicated in disease, but it interacts physically with the HIRA protein (OMIM), which has been linked to DiGeorge syndrome and velocardiofacial syndrome (9).

Last updated: 2008-06-04