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.

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Support Year
9
Fiscal Year
2015
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Name
U.S. National Inst Diabetes/Digst/Kidney
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Rostovtseva, Tatiana K; Gurnev, Philip A; Protchenko, Olga et al. (2015) ?-Synuclein Shows High Affinity Interaction with Voltage-dependent Anion Channel, Suggesting Mechanisms of Mitochondrial Regulation and Toxicity in Parkinson Disease. J Biol Chem 290:18467-77
Cyert, Martha S; Philpott, Caroline C (2013) Regulation of cation balance in Saccharomyces cerevisiae. Genetics 193:677-713
Huynh, Chau; Yuan, Xiaojing; Miguel, Danilo C et al. (2012) Heme uptake by Leishmania amazonensis is mediated by the transmembrane protein LHR1. PLoS Pathog 8:e1002795
Philpott, Caroline C; Leidgens, Sébastien; Frey, Avery G (2012) Metabolic remodeling in iron-deficient fungi. Biochim Biophys Acta 1823:1509-20
Yuan, Xiaojing; Protchenko, Olga; Philpott, Caroline C et al. (2012) Topologically conserved residues direct heme transport in HRG-1-related proteins. J Biol Chem 287:4914-24
Boretsky, Yuriy R; Pynyaha, Yuriy V; Boretsky, Volodymyr Y et al. (2011) Identification of the genes affecting the regulation of riboflavin synthesis in the flavinogenic yeast Pichia guilliermondii using insertion mutagenesis. FEMS Yeast Res 11:307-14