Richard Eisenstein

We work on the control of iron metabolism by iron regulatory proteins (IRP). IRP are cytosolic iron-regulated RNA binding proteins that determine the fate (translation or stability) of at least 9 mRNA in mammals. IRPs are critical for the maintenance of iron homeostasis and the adaptive responsive to iron deficiency. We are interested in how changes in iron status affects tissue fuel metabolism especially during postnatal growth where loss of IRP1 leads to interorgan iron mismanagement and impaired fuel metabolism in heart and perhaps other tissues. We are also interested in the elucidating why IRP control the translation of the mRNA encoding the TCA cycle enzyme mitochondrial aconitase. Our preliminary data indicates this provides a mechanism through which iron status and other effectors of IRP activity dictate changes in the export of citrate by mitochondria. We propose new roles for controlling mitochondrial citrate export beyond fatty acid formation possibly including metabolite-driven changes in hypoxia sensing or perhaps epigenetic regulation. There may be avenues here for a collaborative study on possible actions of IRP-dependent changes in mitochondrial citrate export on beta cell fuel sensing and insulin secretion.