Eukaryotic Heme Utilization

我们对真核生物中血红素的转运知之甚少，在酵母中也没有发现血红素特异性转运摄取系统。虽然酿酒酵母在铁缺乏时不吸收血红素，但我们已经确定，该物种确实具有在血红素缺乏和缺氧条件下激活的诱导血红素摄取系统。我们对在这些条件下生长的菌株进行了微阵列分析，发现许多假定的转运蛋白被转录激活。

Very little is known about heme transport in eukaryotes and a heme-specific transport uptake systems have not been identified in yeast. Although S. cerevisiae does not take up heme in response to iron deprivation, we have determined that this species does have an inducible heme uptake system that is activated under heme deficiency and hypoxic conditions. We performed microarray analysis of strains grown under these conditions, and found that a number of putative transporters are transcriptionally activated. Heme is synthesized in mitochondria, yet the cofactor is used in compartments throughout the cell. Heme is highly hydrophobic and is unlikely to be released into the aqueous environment of the cytosol, suggesting that mechanisms exist for the intracellular trafficking of heme. We have designed a genetic screen for the identification of yeast proteins involved in intracellular heme trafficking and are evaluating candidates. Genes identified in this screen suggest that heme moves from the mitochondria to other sites through the vesicular trafficking system. In collaboration with Iqbal Hamza of the University of Maryland, we are functionally characterizing the putative heme transporters of C. elegans by expressing them in yeast. Heme transporters from C. elegans have heme uptake activity when expressed in yeast and mutant forms of heme transporters exhibit loss of function when expressed in yeast.