Eukaryotic Heme Utilization

人们对真核生物中的血红素转运知之甚少，酵母中也没有鉴定出一种特定的血红素转运系统。血红素是在线粒体中合成的，但辅因子在整个细胞的隔间中使用。血红素是高度疏水的，不太可能被释放到胞浆的水环境中，这表明存在着血红素在细胞内运输的机制。我们目前正在表征人类线粒体血红素出口商FLVCR1b的血红素外流活性。 线粒体外膜电压依赖性阴离子通道VDAC影响血红素在酵母线粒体外的转运。在相关的一系列研究中，我们发现人α-突触核蛋白在酵母中的异位表达影响了酵母VDAC的功能以及在酵母中异位表达的人VDAC的功能。这些研究影响了我们对α-突触核蛋白在帕金森病中致病作用的理解。

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.