In silico analyses of Fsf1 sequences, a new group of fungal proteins orthologous to the metazoan sideroblastic anemia-related sideroflexin family

Sideroblastic anemias are pathologies observed in metazoan species characterized by accumulation of iron in the mitochondria (sideroblasts), defective erythropoiesis, and iron overload. Some genes have been associated with sideroblastic anemia, e.g. δ-aminolevulinic acid synthase gene (e-ALAS2). Recently, a new sideroblastic-associated protein family was discovered in metazoans and termed sideroflexin (Sfxn). The metazoan Sfxn family comprises five groups of paralogous proteins, present in mitochondria and whose functions are unknown. Using an in silico approach, we have identified and characterized new sideroflexin sequences from the genomes of different fungal species. An in-depth phylogenetic analysis of these new fungal Sfxn sequences (termed Fsf1p) showed that they form a distinct clade within the metazoan Sfxn family. Hydrophobic cluster analysis and transmembrane topological mapping allowed us to compare conserved regions among Fsf1 and Sfxn proteins. The results indicate that Fsf1 probably belongs to an ancient, mitochondrial group of proteins, necessary to maintain the homeostasis of iron within this organelle.