Transcriptional regulation and life-span modulation of cytosolic aconitase and ferritin genes in C-elegans

Ferritin is the major iron storage protein regulating cytosolic concentration of iron by storing excess iron. Vertebrate ferritins are heteropolymeric proteins composed of heavy chain and light chain subunits. We have characterized two Caenorhabditis elegans genes (ftn-1 and ftn-2), which encode ferritin homologs showing high degree of similarity to mammalian ferritin heavy chains. Even though these two ferritins are more than 78% identical in amino acid sequence, our data show that expression patterns and responses to iron are quite different. Cytosolic aconitase (aco-1), iron regulatory protein, is known to regulate cellular iron concentration by modulating translation of the ferritin mRNA in addition to its enzymatic activity that converts citrate into iso-citrate. We have shown that the expression levels of aco-1 and ftn-1 genes are both regulated by iron treatment but in opposite ways. Interestingly, mutant animals lacking ACO-1 and FTN-1 show significantly reduced life-span upon iron stress, while N2 and ftn-2 animals show no difference. Our results suggest that ftn-1 and aco-1 are transcriptionally regulated by iron and are important for iron homeostasis affecting life-span upon iron stress conditions in C. elegans. (C) 2004 Elsevier Ltd. All rights reserved.