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Open seminar

Lecture Title "Heme Trafficking from the Ground-Up: Lessons from C. elegans"
Date Friday 29 June 2012 16:00 to 17:00
Lecturer Prof. Iqbal Hamza (University of Maryland, USA)
Place

Yamate Building 3, 2nd floor, Seminar Room
Summary

Heme is a vital but cytotoxic cofactor responsible for diverse biological functions such as gas synthesis and sensing, circadian clock control, microRNA processing, and xenobiotic detoxification.  
Heme synthesis occurs in the mitochondria of nearly all eukaryotes.  
Free heme is a hydrophobic tetracycle and cytotoxic. How then is heme transported through cellular membranes and organelles?  What are the mechanisms for incorporating heme into specific hemoproteins that reside in the cytoplasm, peroxisomes, mitochondria, secretory pathway, and nucleus? Our work with the invertebrate animal model C. elegans has demonstrated that this roundworm is exceptional because it does not synthesize heme but rather utilizes environmental heme to manufacture heme-containing proteins, which have human homologs.  
Genetic screens in C. elegans identified several novel genes which we termed Heme Responsive Genes (HRGs); dietary heme is transported into the worm intestine by membrane-bound permeases, HRG-1 and HRG-4.  
Correspondingly, tissues such as muscle, neurons, hypodermal cells, and embryos are dependent on intestinal heme to fulfill their metabolic requirements.  Consistent with this concept, we uncovered the next piece in the puzzle- HRG-3, a novel peptide secreted by the mother’s intestine and functions to transport maternal heme to developing oocytes ensuring that sufficient heme is available to sustain embryonic development.  These results imply that HRG-3 functions as an intercellular chaperone to mobilize maternal heme and deliver it to extra-intestinal tissues. Our findings represent major discoveries in heme trafficking and establish a paradigm for heme transport in animals.
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AONO, Shigetoshi
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