Eukaryotic Heme Utilization

真核血红素利用

• 批准号: 9148849
• 负责人: Caroline Philpott
• 金额: $ 7.55万
• 依托单位: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9148849
• 关键词: Affect; Binding; Biochemical; Biological; Cells; Copper; Cytosol; Ectopic Expression; Environment; Enzymes; Eukaryota; Friedreich Ataxia; Genes; Genetic; Genetic study; Heme; Heme Iron; Hemoglobin; Hereditary Disease; Hereditary hemochromatosis; Homeostasis; Human; Intracellular Transport; Iron; Iron Compounds; Iron Overload; Mammals; Metabolism; Mitochondria; Myoglobin; Nutrient; Organic Iron Compounds; Organism; Outer Mitochondrial Membrane; Oxygen; Parkinson Disease; Process; Regulation; Role; Saccharomyces cerevisiae; Saccharomycetales; Series; System; Toxin; Voltage-Dependent Anion Channel; Yeasts; Zinc; alpha synuclein; aqueous; cofactor; deprivation; heme a; human disease; insight; iron metabolism; metal metabolism; microorganism; response; synuclein, alpha (non A4 component of amyloid precursor) protein, human; trafficking; uptake

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.

关于血红素在真核生物中的转运知之甚少，并且在酵母中还没有鉴定出血红素特异性转运摄取系统。血红素是在线粒体中合成的，而辅因子则在整个细胞的各个区域中使用。血红素是高度疏水性的，并且不太可能被释放到胞质溶胶的水性环境中，这表明存在血红素的细胞内运输的机制。 我们目前正在表征血红素流出活性的推定线粒体血红素出口的人，FLVCR 1b。 线粒体外膜电压依赖性阴离子通道（VDAC）影响血红素从酵母线粒体的转运。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酵母VDAC的功能和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的致病作用的理解。

项目成果

Identification of the genes affecting the regulation of riboflavin synthesis in the flavinogenic yeast Pichia guilliermondii using insertion mutagenesis.

• DOI: 10.1111/j.1567-1364.2011.00720.x
• 发表时间: 2011-05
• 期刊: FEMS yeast research
• 影响因子: 3.2
• 作者: Boretsky YR;Pynyaha YV;Boretsky VY;Fedorovych DV;Fayura LR;Protchenko O;Philpott CC;Sibirny AA
• 通讯作者: Sibirny AA