This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.In biology, iron plays two contrasting roles. While being an essential element and a necessary structural and functional component of many proteins, iron has the capacity to be a potent cytotoxin. Under physiological conditions, free Fe(II) can generate hydroxyl radicals via Fenton chemistry. These radicals are capable of damaging every cellular component including DNA, proteins and lipid membranes. A great deal is known about the mechanisms of cellular iron uptake and utilization. However, there is a gap in our knowledge regarding the transport of iron from sites of uptake to sites of utilization. We hypothesize that intracellular iron transport is mediated by soluble proteins, metallochaperones, that bind iron at sights of uptake or release and traffic iron to sites of utilization or storage. An analogous system has been described for intracellular copper trafficking. Binding and release of iron by metallochaperones would be mediated by protein-protein interactions; thus, we propose a yeast two-hybrid experiment using the C-terminal cytoplasmic domain of the S. cerevisiae high affinity iron transporter as bait to identify putative iron chaperones in the S. cerevisiae genome.
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