Eukaryotic Heme Utilization

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Very little is known about heme transport in eukaryotes and a heme-specific transport uptake systems have not been identified in yeast. 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 are currently characterizing the heme efflux activity of the putative mitochondrial heme exporter of humans, FLVCR1b. The mitochondrial outer membrane voltage-dependent anion channel, VDAC, affects the transport of heme out of the mitochondria of yeast. In a related series of studies, we found that ectopic expression of human alpha-synuclein in yeast affected the function of yeast VDAC and the function of human VDAC that was ectopically expressed in yeast. These studies affect our understanding of the pathogenic role of alpha-synuclein in Parkinson Disease.