title: Modeling human Coenzyme A synthase mutation in yeast reveals altered mitochondrial function, lipid content and iron metabolism.
abstract: Mutations in nuclear genes associated with defective coenzyme A biosynthesis have been identified as responsible for some forms of neurodegeneration with brain iron accumulation (NBIA), namely PKAN and CoPAN. PKAN are defined by mutations inPANK2, encoding the pantothenate kinase 2 enzyme, that account for about 50% of cases of NBIA, whereas mutations in CoA synthaseCOASYhave been recently reported as the second inborn error of CoA synthesis leading to CoPAN. As reported previously, yeast cells expressing the pathogenic mutation exhibited a temperature-sensitive growth defect in the absence of pantothenate and a reduced CoA content. Additional characterization revealed decreased oxygen consumption, reduced activities of mitochondrial respiratory complexes, higher iron content, increased sensitivity to oxidative stress and reduced amount of lipid droplets, thus partially recapitulating the phenotypes found in patients and establishing yeast as a potential model to clarify the pathogenesis underlying PKAN and CoPAN diseases.
authors.affiliation: Department of Life Sciences, University of Parma, Parma, Italy.
authors.forename: Camilla
authors.initials: C
authors.lastname: Ceccatelli  Berti
authors.affiliation: Department of Life Sciences, University of Parma, Parma, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Dallabona
authors.affiliation: Department of Life Sciences, University of Parma, Parma, Italy.
authors.forename: Mirca
authors.initials: M
authors.lastname: Lazzaretti
authors.affiliation: Unit of Molecular Neurogenetics - Pierfranco and Luisa Mariani Center for the study of Mitochondrial Disorders in Children, IRCCS Foundation Neurological Institute "C. Besta", Milan, Italy.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Dusi
authors.affiliation: Department of Life Sciences, University of Parma, Parma, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Tosi
authors.affiliation: Unit of Molecular Neurogenetics - Pierfranco and Luisa Mariani Center for the study of Mitochondrial Disorders in Children, IRCCS Foundation Neurological Institute "C. Besta", Milan, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Tiranti
authors.affiliation: Department of Life Sciences, University of Parma, Parma, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Goffrini
keywords: COASY; Coenzyme A; NBIA; Saccharomyces cerevisiae; iron accumulation; lipid content; mitochondria; yeast model