Modeling human Coenzyme A synthase mutation in yeast reveals altered mitochondrial function, lipid content and iron metabolism
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 in PANK2, encoding the pantothenate kinase 2 enzyme...
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| Format: | Article |
| Language: | English |
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Shared Science Publishers OG
2015-04-01
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| Series: | Microbial Cell |
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| Online Access: | http://microbialcell.com/researcharticles/modeling-human-coenzyme-a-synthase-mutation-in-yeast-reveals-altered-mitochondrial-function-lipid-content-and-iron-metabolism-2/ |
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| author | Camilla Ceccatelli Berti Cristina Dallabona Mirca Lazzaretti Sabrina Dusi Elena Tosi Valeria Tiranti Paola Goffrini |
| author_facet | Camilla Ceccatelli Berti Cristina Dallabona Mirca Lazzaretti Sabrina Dusi Elena Tosi Valeria Tiranti Paola Goffrini |
| author_sort | Camilla Ceccatelli Berti |
| collection | DOAJ |
| description | 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 in PANK2, encoding the pantothenate kinase 2 enzyme, that account for about 50% of cases of NBIA, whereas mutations in CoA synthase COASY have 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. |
| first_indexed | 2024-12-11T08:04:07Z |
| format | Article |
| id | doaj.art-55deefbd69e14a4099be894d9dc25a57 |
| institution | Directory Open Access Journal |
| issn | 2311-2638 |
| language | English |
| last_indexed | 2024-12-11T08:04:07Z |
| publishDate | 2015-04-01 |
| publisher | Shared Science Publishers OG |
| record_format | Article |
| series | Microbial Cell |
| spelling | doaj.art-55deefbd69e14a4099be894d9dc25a572022-12-22T01:15:03ZengShared Science Publishers OGMicrobial Cell2311-26382015-04-012412613510.15698/mic2015.04.196123455678Modeling human Coenzyme A synthase mutation in yeast reveals altered mitochondrial function, lipid content and iron metabolismCamilla Ceccatelli Berti0Cristina Dallabona1Mirca Lazzaretti2Sabrina Dusi3Elena Tosi4Valeria Tiranti5Paola Goffrini6Department of Life Sciences, University of Parma, Parma, Italy.Department of Life Sciences, University of Parma, Parma, Italy.Department of Life Sciences, University of Parma, Parma, Italy.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.Department of Life Sciences, University of Parma, Parma, Italy.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.Department of Life Sciences, University of Parma, Parma, Italy.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 in PANK2, encoding the pantothenate kinase 2 enzyme, that account for about 50% of cases of NBIA, whereas mutations in CoA synthase COASY have 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.http://microbialcell.com/researcharticles/modeling-human-coenzyme-a-synthase-mutation-in-yeast-reveals-altered-mitochondrial-function-lipid-content-and-iron-metabolism-2/Saccharomyces cerevisiaeyeast modelCoenzyme ANBIACOASYmitochondriairon accumulationlipid content |
| spellingShingle | Camilla Ceccatelli Berti Cristina Dallabona Mirca Lazzaretti Sabrina Dusi Elena Tosi Valeria Tiranti Paola Goffrini Modeling human Coenzyme A synthase mutation in yeast reveals altered mitochondrial function, lipid content and iron metabolism Microbial Cell Saccharomyces cerevisiae yeast model Coenzyme A NBIA COASY mitochondria iron accumulation lipid content |
| title | Modeling human Coenzyme A synthase mutation in yeast reveals altered mitochondrial function, lipid content and iron metabolism |
| title_full | Modeling human Coenzyme A synthase mutation in yeast reveals altered mitochondrial function, lipid content and iron metabolism |
| title_fullStr | Modeling human Coenzyme A synthase mutation in yeast reveals altered mitochondrial function, lipid content and iron metabolism |
| title_full_unstemmed | Modeling human Coenzyme A synthase mutation in yeast reveals altered mitochondrial function, lipid content and iron metabolism |
| title_short | Modeling human Coenzyme A synthase mutation in yeast reveals altered mitochondrial function, lipid content and iron metabolism |
| title_sort | modeling human coenzyme a synthase mutation in yeast reveals altered mitochondrial function lipid content and iron metabolism |
| topic | Saccharomyces cerevisiae yeast model Coenzyme A NBIA COASY mitochondria iron accumulation lipid content |
| url | http://microbialcell.com/researcharticles/modeling-human-coenzyme-a-synthase-mutation-in-yeast-reveals-altered-mitochondrial-function-lipid-content-and-iron-metabolism-2/ |
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