Ferritins are iron storage proteins whose expression in vertebrates is. regulated at both the transcriptional and post-transcriptional levels. C.. elegans has two genes encoding ferritins, both heavy chains,
ftn-1 and ftn-. 2. Exposure to iron induces expression of
ftn-1 and, to a lesser extent,.
ftn-2. We report that
ftn-1 (but not
ftn-2) mRNA levels are also strongly. elevated in long-lived
daf-2 insulin/IGF-1 receptor mutants. This induction. is dependent on the FOXO transcription factor DAF-16. This pattern of. regulation was confirmed using a newly constructed
pftn-1::gfp transgenic. line, and occurred largely in the intestine. Free iron increases production. of reactive oxygen species (ROS) in vivo via the Fenton reaction. This. suggests the hypothesis that up-regulation of expression of
ftn-1. contributes to
daf-2 mutant longevity. We are testing this using several. approaches. Firstly, we are employing a hormesis-type approach, using iron. exposure to induce
ftn-1 expression, and then testing for increased. resistance to iron toxicity and retarded aging. Secondly, we are using. genetic means to manipulate
ftn-1 expression levels and then look at the. effects on aging. The progress of these studies will be reported.. Vertebrate ferritins are post-transcriptionally regulated by the binding of. the iron-response protein (IRP) to the 5'' UTR of the ferritin mRNA. ACO-1,. the C. elegans homolog of IRP, has previously been shown to be incapable of. binding
ftn-1 mRNA. Consistent with this, we find that mutational loss of.
aco-1 does not block induction of
ftn-1 expression by exposure to iron or. by attenuation of
daf-2. However, loss of
aco-1 does slightly increase. overall levels of
ftn-1 expression. Thus, despite its inability to bind to. the 5'' UTR of
ftn-1 mRNA, ACO-1 weakly represses
ftn-1 expression,. presumably by some other mechanism.