Modeling human Coenzyme A synthase mutation in yeast reveals altered mitochondrial function, lipid content and iron metabolism
Authors:Camilla Ceccatelli Berti1, Cristina Dallabona1, Mirca Lazzaretti1, Sabrina Dusi2, Elena Tosi1, Valeria Tiranti2, Paola Goffrini1
doi: 10.15698/mic2015.04.196
Volume 2, pp. 126 to 135, published 06/04/2015.
1 Department of Life Sciences, University of Parma, Parma, Italy.
2 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.
Keywords:
Saccharomyces cerevisiae, yeast model, Coenzyme A, NBIA, COASY, mitochondria, iron accumulation, lipid content
Corresponding Author(s):
Conflict of interest statement:
The authors declare no conflict of interest.
Please cite this article as:
Camilla Ceccatelli Berti, Cristina Dallabona, Mirca Lazzaretti, Sabrina Dusi, Elena Tosi, Valeria Tiranti, Paola Goffrini (2015). Modeling human Coenzyme A synthase mutation in yeast reveals altered mitochondrial function, lipid content and iron metabolism. Microbial Cell 2(4): 126-135.
© 2015 Ceccatelli Berti et al. This is an open-access article released under the terms of the Creative Commons Attribution (CC BY) license, which allows the unrestricted use, distribution, and reproduction in any medium, provided the original author and source are acknowledged.
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 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.