title: Mitochondrial Carriers Link the Catabolism of Hydroxyaromatic Compounds to the Central Metabolism in Candida parapsilosis.
abstract: The pathogenic yeast Candida parapsilosis metabolizes hydroxyderivatives of benzene and benzoic acid to compounds channeled into central metabolism, including the mitochondrially localized tricarboxylic acid cycle, via the 3-oxoadipate and gentisate pathways. The orchestration of both catabolic pathways with mitochondrial metabolism as well as their evolutionary origin is not fully understood. Our results show that the enzymes involved in these two pathways operate in the cytoplasm with the exception of the mitochondrially targeted 3-oxoadipate CoA-transferase (Osc1p) and 3-oxoadipyl-CoA thiolase (Oct1p) catalyzing the last two reactions of the 3-oxoadipate pathway. The cellular localization of the enzymes indicates that degradation of hydroxyaromatic compounds requires a shuttling of intermediates, cofactors, and products of the corresponding biochemical reactions between cytosol and mitochondria. Indeed, we found that yeast cells assimilating hydroxybenzoates increase the expression of genes SFC1, LEU5, YHM2, and MPC1 coding for succinate/fumarate carrier, coenzyme A carrier, oxoglutarate/citrate carrier, and the subunit of pyruvate carrier, respectively. A phylogenetic analysis uncovered distinct evolutionary trajectories for sparsely distributed gene clusters coding for enzymes of both pathways. Whereas the 3-oxoadipate pathway appears to have evolved by vertical descent combined with multiple losses, the gentisate pathway shows a striking pattern suggestive of horizontal gene transfer to the evolutionarily distant Mucorales.
authors.affiliation: Department of Biochemistry, Comenius University in Bratislava, Faculty of Natural Sciences, 842 15, Slovak Republic nosek@fns.uniba.sk.
authors.forename: Igor
authors.initials: I
authors.lastname: Zeman
authors.affiliation: Department of Biochemistry, Comenius University in Bratislava, Faculty of Natural Sciences, 842 15, Slovak Republic.
authors.forename: Martina
authors.initials: M
authors.lastname: Neboháčová
authors.affiliation: Department of Biochemistry, Comenius University in Bratislava, Faculty of Natural Sciences, 842 15, Slovak Republic.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Gérecová
authors.affiliation: Department of Biochemistry, Comenius University in Bratislava, Faculty of Natural Sciences, 842 15, Slovak Republic.
authors.forename: Kornélia
authors.initials: K
authors.lastname: Katonová
authors.affiliation: Department of Biochemistry, Comenius University in Bratislava, Faculty of Natural Sciences, 842 15, Slovak Republic.
authors.forename: Eva
authors.initials: E
authors.lastname: Jánošíková
authors.affiliation: Department of Biochemistry, Comenius University in Bratislava, Faculty of Natural Sciences, 842 15, Slovak Republic.
authors.forename: Michaela
authors.initials: M
authors.lastname: Jakúbková
authors.affiliation: Department of Biochemistry, Comenius University in Bratislava, Faculty of Natural Sciences, 842 15, Slovak Republic.
authors.forename: Ivana
authors.initials: I
authors.lastname: Centárová
authors.affiliation: Department of Biochemistry, Comenius University in Bratislava, Faculty of Natural Sciences, 842 15, Slovak Republic.
authors.forename: Ivana
authors.initials: I
authors.lastname: Dunčková
authors.affiliation: Department of Genetics, Comenius University in Bratislava, Faculty of Natural Sciences, 842 15, Slovak Republic.
authors.forename: L'ubomír
authors.identifier: 0000-0003-4886-1910
authors.initials: L
authors.lastname: Tomáška
authors.affiliation: Bioinformatics and Genomics Programme, Centre for Genomic Regulation, 08003 Barcelona, Spain.
authors.forename: Leszek P
authors.initials: LP
authors.lastname: Pryszcz
authors.affiliation: Bioinformatics and Genomics Programme, Centre for Genomic Regulation, 08003 Barcelona, Spain.|Departament de Ciències Experimentals I de la Salut, Universitat Pompeu Fabra, 08003 Barcelona, Spain.|Institució Catalana de Recerca i Estudis Avançats, 08010 Barcelona, Spain.
authors.forename: Toni
authors.identifier: 0000-0003-0019-1735
authors.initials: T
authors.lastname: Gabaldón
authors.affiliation: Department of Biochemistry, Comenius University in Bratislava, Faculty of Natural Sciences, 842 15, Slovak Republic nosek@fns.uniba.sk.
authors.forename: Jozef
authors.identifier: 0000-0002-1020-5451
authors.initials: J
authors.lastname: Nosek
mesh_terms: D000102:Acetyl-CoA C-Acyltransferase / Q000235:genetics / Q000378:metabolism; D001203:Ascomycota / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D005075:Biological Evolution; D015256:Coenzyme A-Transferases / Q000235:genetics / Q000378:metabolism; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D006841:Hydrocarbons, Aromatic / Q000378:metabolism*; D053858:Metabolic Networks and Pathways; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D010802:Phylogeny; D021381:Protein Transport; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D013379:Substrate Specificity
chemical_list: D005656:Fungal Proteins; D006841:Hydrocarbons, Aromatic; D000102:Acetyl-CoA C-Acyltransferase; C443987:3-oxoadipyl-coenzyme A thiolase; D015256:Coenzyme A-Transferases; C028573:3-oxoadipate CoA-transferase
keywords: 3-oxoadipate pathway; catabolism of hydroxybenzoates; evolution of biochemical pathways; gentisate pathway; mitochondrial carrier